The Virus

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12/04/2021 Articles
Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SAR...

Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV

NATURE

Authors
Alexey Stukalov, Virginie Girault, Vincent Grass, Ozge Karayel, Valter Bergant, Christian Urban, Darya A. Haas, Yiqi Huang, Lila Oubraham, Anqi Wang, M. Sabri Hamad, Antonio Piras, Fynn M. Hansen, Maria C. Tanzer, Igor Paron, Luca Zinzula, Thomas Enghleitner, Maria Reinecke, Teresa M. Lavacca, Rosina Ehmann, Roman Wölfel, Jörg Jores, Bernhard Kuster, Ulrike Protzer, Roland Rad, John Ziebuhr, Volker Thiel, Pietro Scaturro, Matthias Mann, Andreas Pichlmair

Abstract
The global emergence of SARS-CoV-2 urgently requires an in-depth understanding of molecular functions of viral proteins and their interactions with the host proteome. Several individual omics studies have extended our knowledge of COVID-19 pathophysiology1–10. Integration of such datasets to obtain a holistic view of virus-host interactions and to define the pathogenic properties of SARS-CoV-2 is limited by the heterogeneity of the experimental systems. We therefore conducted a concurrent multi-omics study of SARS-CoV-2 and SARS-CoV. Using state-of-the-art proteomics, we profiled the interactome of both viruses, as well as their influence on transcriptome, proteome, ubiquitinome and phosphoproteome in a lung-derived human cell line. Projecting these data onto the global network of cellular interactions revealed crosstalk between the perturbations taking place upon SARS-CoV-2 and SARS-CoV infections at different layers and identified unique and common molecular mechanisms of these closely related coronaviruses. The TGF-β pathway, known for its involvement in tissue fibrosis, was specifically dysregulated by SARS-CoV-2 ORF8 and autophagy by SARS-CoV-2 ORF3. The extensive dataset (available at https://covinet.innatelab.org) highlights many hotspots that can be targeted by existing drugs and it can guide rational design of virus- and host-directed therapies, which we exemplify by identifying kinase and MMPs inhibitors with potent antiviral effects against SARS-CoV-2.

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09/04/2021 Articles
Rise of Variants in Europe Shows How Dangerous the Virus Can Be

THE NEW YORK TIMES

Authors
Josh Holder, Allison McCann, Benjamin Mueller

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06/04/2021 New Result
Unique protein features of SARS-CoV-2 relative to other Sarbecoviruses

BIORXIV

Authors
Matthew Cotten, David L. Robertson, V.T. Phan

Abstract
Defining the unique protein features of SARS-CoV-2, the viral agent causing Coronavirus Disease 2019, may guide efforts to control this pathogen. We examined proteins encoded by the Sarbecoviruses closest to SARS-CoV-2 using profile Hidden Markov Model similarities to identify features unique to SARS-CoV-2. Consistent with previous reports, a small set of bat and pangolin-derived Sarbecoviruses show the greatest similarity to SARS-CoV-2. The analysis provided a measure of total proteome similarity and showed that a small subset of bat Sarbecoviruses are closely related but unlikely to be the direct source of SARS-CoV-2. Spike analysis reveals that the current SARS-CoV-2 variants of concern have sampled only 36% of the possible spikes changes which have occurred historically in Sarbecovirus evolution. It is likely that new SARS-CoV-2 variants with changes in these regions are compatible with virus replication and are to be expected in the coming months, unless global viral replication is severely reduced.

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05/04/2021 Articles
Community Transmission of SARS-CoV-2 Associated with a Local Bar Openi...

Community Transmission of SARS-CoV-2 Associated with a Local Bar Opening Event — Illinois, February 2021

CDC (CENTERS FOR DISEASE CONTROL AND PREVENTION)

Authors
Samira Sami, Caitlin R. Turbyfill, Shelby Daniel-Wayman, Stacy Shonkwiler, Kiva A. Fisher; Macey Kuhring; Aaron M. Patrick; Stephanie Hinton, Amanda S. Minor, Jessica N. Ricaldi, Ngozi Ezike, Judy Kauerauf, Wayne A. Duffus

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04/04/2021 Articles
Troubling "Eek" variant found in most Tokyo hospital COVID cases - NHK

REUTERS

Authors
Reuters Staff

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01/04/2021 Articles
Computational epitope map of SARS-CoV-2 spike protein

PLOS

Authors
Mateusz SikoraI, So ̈ren von Bu ̈lowI, Florian E. C. BlancI, Michael GechtI, Roberto CovinoI, Gerhard HummerI

Abstract
The primary immunological target of COVID-19 vaccines is the SARS-CoV-2 spike (S) protein. S is exposed on the viral surface and mediates viral entry into the host cell. To identify possible antibody binding sites, we performed multi-microsecond molecular dynamics simulations of a 4.1 million atom system containing a patch of viral membrane with four full-length, fully glycosylated and palmitoylated S proteins. By mapping steric accessibility, structural rigidity, sequence conservation, and generic antibody binding signatures, we recover known epitopes on S and reveal promising epitope candidates for structure-based vaccine design. We find that the extensive and inherently flexible glycan coat shields a surface area larger than expected from static structures, highlighting the importance of structural dynamics. The protective glycan shield and the high flexibility of its hinges give the stalk overall low epitope scores. Our computational epitope-mapping procedure is general and should thus prove useful for other viral envelope proteins whose structures have been characterized.

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29/03/2021 Case Report
Risk of SARS-CoV-2 transmission from ne...nted previous infection or v...

Risk of SARS-CoV-2 transmission from ne...nted previous infection or vaccination

ECDC

Authors
ECDC (European Centre for Disease Prevention and Control)

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26/03/2021 Viewpoint
The emerging plasticity of SARS-CoV-2

SCIENCE

Authors
Kevin D. McCormick, Jana L. Jacobs, John W. Mellors

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22/03/2021 Articles
Transmissibility and transmission of respiratory viruses

NATURE

Authors
Nancy H. L. Leung

Abstract
Human respiratory virus infections lead to a spectrum of respiratory symptoms and disease severity, contributing to substantial morbidity, mortality and economic losses worldwide, as seen in the COVID-19 pandemic. Belonging to diverse families, respiratory viruses differ in how easy they spread (transmissibility) and the mechanism (modes) of transmission. Transmissibility as estimated by the basic reproduction number (R0) or secondary attack rate is heterogeneous for the same virus. Respiratory viruses can be transmitted via four major modes of transmission: direct (physical) contact, indirect contact (fomite), (large) droplets and (fine) aerosols. We know little about the relative contribution of each mode to the transmission of a particular virus in different settings, and how its variation affects transmissibility and transmission dynamics. Discussion on the particle size threshold between droplets and aerosols and the importance of aerosol transmission for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus is ongoing. Mechanistic evidence supports the efficacies of non-pharmaceutical interventions with regard to virus reduction; however, more data are needed on their effectiveness in reducing transmission. Understanding the relative contribution of different modes to transmission is crucial to inform the effectiveness of non-pharmaceutical interventions in the population. Intervening against multiple modes of transmission should be more effective than acting on a single mode.

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18/03/2021 New Result
12 Months of COVID-19 Eliminated 12 Years of Progress in the Global Fi...

12 Months of COVID-19 Eliminated 12 Years of Progress in the Global Fight Against Tuberculosis\

STOP TB PARTNERSHIP

Authors
Stop TB PARTNERSHIP

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12/03/2021 Articles
Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced ...

Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity

CELL

Authors
Wilfredo F. Garcia-Beltran, Evan C. Lam, Kerri St. Denis, Adam D. Nitido, Zeidy H. Garcia, Blake M. Hauser, Jared Feldman, Maia N. Pavlovic, David J. Gregory, Mark C. Poznansky, Alex Sigal, Aaron G. Schmidt, A. John Iafrate, Vivek Naranbhai, Alejandro B. Balazs

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08/03/2021 Articles
Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7

NATURE

Authors
Pengfei Wang, Manoj S. Nair, Lihong Liu, Sho Iketani, Yang Luo, Yicheng Guo, Maple Wang, Jian Yu, Baoshan Zhang, Peter D. Kwong, Barney S. Graham, John R. Mascola, Jennifer Y. Chang, Michael T. Yin, Magdalena Sobieszczyk, Christos A. Kyratsous, Lawrence Shapiro, Zizhang Sheng, Yaoxing Huang, David D. Ho

Abstract
The COVID-19 pandemic has ravaged the globe, and its causative agent, SARS-CoV-2, continues to rage. The prospects of ending this pandemic rest on the development of effective interventions. Single and combination monoclonal antibody (mAb) therapeutics have received emergency use authorization1–3, with more in the pipeline4–7. Furthermore, multiple vaccine constructs have shown promise8, including two with ~95% protective efficacy against COVID-199,10. However, these interventions were directed toward the initial SARS-CoV-2 that emerged in 2019. The recent emergence of new SARS-CoV-2 variants B.1.1.7 in the UK11 and B.1.351 in South Africa12 is of concern because of their purported ease of transmission and extensive mutations in the spike protein. We now report that B.1.1.7 is refractory to neutralization by most mAbs to the N-terminal domain (NTD) of the spike and relatively resistant to a few mAbs to the receptor-binding domain (RBD). It is not more resistant to convalescent plasma or vaccinee sera. Findings on B.1.351 are more worrisome in that this variant is not only refractory to neutralization by most NTD mAbs but also by multiple individual mAbs to the receptor-binding motif on RBD, largely owing to an E484K mutation. Moreover, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4 fold) and vaccinee sera (10.3-12.4 fold). B.1.351 and emergent variants13,14 with similar spike mutations present new challenges for mAb therapy and threaten the protective efficacy of current vaccines.

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04/03/2021 Articles
Resistance of SARS-CoV-2 variants to neutralization by monoclonal and ...

Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies

NATURE

Authors
Rita E. Chen, Xianwen Zhang, James Brett Case, Emma S. Winkler, Yang Liu, Laura A. VanBlargan, Jianying Liu, John M. Errico, Xuping Xie, Naveenchandra Suryadevara, Pavlo Gilchuk, Seth J. Zost, Stephen Tahan, Lindsay Droit, Jackson S. Turner, Wooseob Kim, Aaron J. Schmitz, Mahima Thapa, David Wang, Adrianus C. M. Boon, Rachel M. Presti, Jane A. O’Halloran, Alfred H. J. Kim, Parakkal Deepak, Dora Pinto, Daved H. Fremont, James E. Crowe Jr, Davide Corti, Herbert W. Virgin, Ali H. Ellebedy, Pei-Yong Shi, Michael S. Diamond

Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global COVID-19 pandemic. Rapidly spreading SARS-CoV-2 variants may jeopardize newly introduced antibody and vaccine countermeasures. Here, using monoclonal antibodies (mAbs), animal immune sera, human convalescent sera and human sera from recipients of the BNT162b2 mRNA vaccine, we report the impact on antibody neutralization of a panel of authentic SARS-CoV-2 variants including a B.1.1.7 isolate, chimeric strains with South African or Brazilian spike genes and isogenic recombinant viral variants. Many highly neutralizing mAbs engaging the receptor-binding domain or N-terminal domain and most convalescent sera and mRNA vaccine-induced immune sera showed reduced inhibitory activity against viruses containing an E484K spike mutation. As antibodies binding to spike receptor-binding domain and N-terminal domain demonstrate diminished neutralization potency in vitro against some emerging variants, updated mAb cocktails targeting highly conserved regions, enhancement of mAb potency or adjustments to the spike sequences of vaccines may be needed to prevent loss of protection in vivo.

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04/03/2021 Original Investigation
SARS-CoV-2 on Ocular Surfaces in a Cohort of Patients With COVID-19 Fr...

SARS-CoV-2 on Ocular Surfaces in a Cohort of Patients With COVID-19 From the Lombardy Region, Italy

JAMA

Authors
Claudio Azzolini, Simone Donati, Elias Premi, Andreina Baj, Claudia Siracusa, Angelo Genoni, Paolo A. Grossi, Lorenzo Azzi, Fausto Sessa, Francesco Dentali, Paolo Severgnini, Giulio Minoja, Luca Cabrini, Maurizio Chiaravalli, Giovanni Veronesi, Giulio Carcano, Lorenzo S. Maffioli, Angelo Tagliabue

Abstract
Importance Since February 2020, coronavirus disease 2019 (COVID-19) has spread rapidly all over the world, with an epidemiological cluster in Lombardy, Italy. The viral communicability may be mediated by various body fluids, but insufficient information is available on the presence of the virus in human tears.

Objectives To investigate the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in tears collected from patients with COVID-19 by means of real-time reverse transcriptase–polymerase chain reaction (rRT-PCR) assay and to assess the association of virus presence with concomitant clinical conditions.

Design, Setting, and Participants Cross-sectional study conducted between April 9 and May 5, 2020. The setting was intensive care units at Azienda Socio-Sanitaria Territoriale (ASST) Sette-Laghi Hospital, University of Insubria, in Varese, Lombardy, Italy. A conjunctival swab was performed in 91 patients hospitalized for COVID-19, which was clinically diagnosed by rRT-PCR assay on nasopharyngeal swabs and by radiological imaging. Conjunctival swabs from 17 additional healthy volunteer participants with no symptoms of COVID-19 were examined to evaluate the availability and applicability of the conjunctival swab test.

Exposure SARS-CoV-2 detection by means of rRT-PCR assay performed on the collected samples obtained by conjunctival swabs.

Main Outcomes and Measures Conjunctival swab and nasopharyngeal swab results are reported, as well as demographic and clinical data.

Results A total of 108 participants (mean [SD] age, 58.7 [14.2] years; 55 female and 53 male) were tested for SARS-CoV-2 using rRT-PCR assay, including 91 patients hospitalized with COVID-19 and 17 were healthy volunteers. SARS-CoV-2 was found on the ocular surface in 52 of 91 patients with COVID-19 (57.1%; 95% CI, 46.3%-67.5%), with a wide variability in the mean viral load from both eyes. Among a subset of 41 patients, concordance of 63.0% (95% CI, 41.0%-81.0%) was found between positive conjunctival and nasopharyngeal swab test results when performed within 2 days of each other. In 17 of these patients, nasopharyngeal swab results were negative for SARS-CoV-2. In 10 of these 17 patients, conjunctival swab results were positive for the virus.

Conclusions and Relevance In this study, SARS-CoV-2 RNA was found on the ocular surface in a large part of this cohort of patients with COVID-19, although the infectivity of this material could not be determined. Because patients may have positive test results with a conjunctival swab and negative results with a nasopharyngeal swab, use of the slightly invasive conjunctival swab may be considered as a supplementary diagnostic test.

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03/03/2021 Viewpoint
The Potential Future of the COVID-19 Pandemic Will SARS-CoV-2 Become a...

The Potential Future of the COVID-19 Pandemic Will SARS-CoV-2 Become a Recurrent Seasonal Infection?

JAMA

Authors
Christopher J. L. Murray, Peter Piot

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26/02/2021 Articles
SARS-CoV-2 spike D614G change enhances replication and transmission

NATURE

Authors
Bin Zhou, Tran Thi Nhu Thao, Donata Hoffmann, Adriano Taddeo, Nadine Ebert, Fabien Labroussaa, Anne Pohlmann, Jacqueline King, Silvio Steiner, Jenna N. Kelly, Jasmine Portmann, Nico Joel Halwe, Lorenz Ulrich, Bettina Salome Trüeb, Xiaoyu Fan, Bernd Hoffmann, Li Wang, Lisa Thomann, Xudong Lin, Hanspeter Stalder, Berta Pozzi, Simone de Brot, Nannan Jiang, Dan Cui, Jaber Hossain, Malania Wilson, Matthew Keller, Thomas J. Stark, John R. Barnes, Ronald Dijkman, Joerg Jores, Charaf Benarafa, David E. Wentworth, Volker Thiel, Martin Beer

Abstract
During the evolution of SARS-CoV-2 in humans a D614G substitution in the spike (S) protein emerged and became the predominant circulating variant (S-614G) of the COVID-19 pandemic1. However, whether the increasing prevalence of the S-614G variant represents a fitness advantage that improves replication and/or transmission in humans or is merely due to founder effects remains elusive. Here, we generated isogenic SARS-CoV-2 variants and demonstrate that the S-614G variant has (i) enhanced binding to human host cell surface receptor angiotensin-converting enzyme 2 (ACE2), (ii) increased replication in primary human bronchial and nasal airway epithelial cultures as well as in a novel human ACE2 knock-in mouse model, and (iii) markedly increased replication and transmissibility in hamster and ferret models of SARS-CoV-2 infection. Collectively, our data show that while the S-614G substitution results in subtle increases in binding and replication in vitro, it provides a real competitive advantage in vivo, particularly during the transmission bottle neck, providing an explanation for the global predominance of S-614G variant among the SARS-CoV-2 viruses currently circulating.

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26/02/2021 PERSPECTIVE
SARS-CoV-2 dependence on host pathways

SCIENCE

Authors
Jason P. Wong, Blossom Damania

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23/02/2021 Articles
One Year of SARS-CoV-2 Evolution

ONE YEAR OF SARS-COV-2 EVOLUTION

Authors
Aiping Wu, Lulan Wang, Hang-Yu Zhou, Cheng-Yang Ji, Shang Zhou Xia, Yang Cao, Jing Meng, Xiao Ding, Sarah Gold, Taijiao Jiang, Genhong Cheng

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23/02/2021 Original Investigation
Densely sampled viral trajectories suggest longer duration of acute in...

Densely sampled viral trajectories suggest longer duration of acute infection with B.1.1.7 variant relative to non-B.1.1.7 SARS-CoV-2

HARVARD LIBRARY

Authors
Stephen M. Kissler, Joseph R. Fauver, Christina Mack, Caroline G. Tai, Mallery I. Breban, Anne E. Watkins, Radhika M. Samant, Deverick J. Anderson, David D. Ho, Nathan D. Grubaugh, Yonatan H. Grad

Abstract
To test whether acute infection with B.1.1.7 is associated with higher or more sustained nasopharyngeal viral concentrations, we assessed longitudinal PCR tests performed in a cohort of 65 individuals infected with SARS-CoV-2 undergoing daily surveillance testing, including seven in fected with B.1.1.7. For individuals infected with B.1.1.7, the mean duration of the proliferation phase was 5.3 days (90% credible interval [2.7, 7.8]), the mean duration of the clearance phase was 8.0 days [6.1, 9.9], and the mean overall duration of infection (proliferation plus clearance) was 13.3 days [10.1, 16.5]. These compare to a mean proliferation phase of 2.0 days [0.7, 3.3], a mean clearance phase of 6.2 days [5.1, 7.1], and a mean duration of infection of 8.2 days [6.5, 9.7] for non-B.1.1.7 virus. The peak viral concentration for B.1.1.7 was 19.0 Ct [15.8, 22.0] compared to 20.2 Ct [19.0, 21.4] for non-B.1.1.7. This converts to 8.5 log10 RNA copies/ml [7.6, 9.4] for B.1.1.7 and 8.2 log10 RNA copies/ml [7.8, 8.5] for non-B.1.1.7. These data offer evidence that SARS-CoV-2 variant B.1.1.7 may cause longer infections with similar peak viral concentration compared to non-B.1.1.7 SARS-CoV-2. This extended duration may contribute to B.1.1.7 SARS CoV-2’s increased transmissibility.

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13/02/2021 Articles
The antigenic anatomy of SARS-CoV-2 receptor binding domain

CELL

Authors
Wanwisa Dejnirattisai, Daming Zhou, Helen M. Ginn, Helen M.E. Duyvesteyn, Piyada Supasa, James Brett Case, Yuguang Zhao, Thomas S. Walter, Alexander J. Mentzer, Chang Liu, Beibei Wang, Guido C. Paesen, Jose Slon-Campos, César López-Camacho, Natasha M. Kafai, Adam L. Bailey, Rita E. Chen, Baoling Ying, Craig Thompson, Jai Bolton, Alex Fyfe, Sunetra Gupta, Tiong Kit Tan, Javier Gilbert- Jaramillo, William James, Michael Knight, Miles W. Carroll, Donal Skelly, Christina Dold, Yanchun Peng, Robert Levin, Tao Dong, Andrew J. Pollard, Julian C. Knight, Paul Klenerman, Nigel Temperton, David R. Hall, Mark A. Williams, Neil G. Paterson, Felicity K.R. Bertram, C. Alistair Seibert, Daniel K. Clare, Andrew Howe, Julika Raedecke, Yun Song, Alain R. Townsend, Kuan-Ying A. Huang, Elizabeth E. Fry, Juthathip Mongkolsapaya, Michael S. Diamond, Jingshan Ren, David I. Stuart, Gavin R. Screaton

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11/02/2021 Letter
Emergence of a Novel SARS-CoV-2 Variant in Southern California

JAMA

Authors
Wenjuan Zhang, Brian D. Davis, Stephanie S. Chen, Jorge M. Sincuir Martinez, Jasmine T. Plummer, Eric Vail

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11/02/2021 Comment
SARS-CoV-2 variants and ending the COVID-19 pandemic

THE LANCET

Authors
Arnaud Fontanet, Brigitte Autran, Bruno Lina, Marie Paule Kieny, Salim S Abdool Karim, Devi Sridhar

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11/02/2021 Editorial
SARS-CoV-2 Viral Variants—Tackling a Moving Target

JAMA

Authors
John R. Mascola, Barney S. Graham, Anthony S. Fauci

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10/02/2021 PERSPECTIVE
Experts Discuss COVID-19—Vaccine Questions, School Openings, and More

JAMA

Authors
Rochelle P. Walensky, Paul A. Offit, Christopher W. Seymour, Arnold S. Monto, Nicholas Christakis

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10/02/2021 Letter
Imported SARS-COV-2 Variant P.1 Detected in Traveler Returning from Br...

Imported SARS-COV-2 Variant P.1 Detected in Traveler Returning from Brazil to Italy

CDC (CENTERS FOR DISEASE CONTROL AND PREVENTION)

Authors
Fabrizio Maggi, Federica Novazzi, Angelo Genoni, Andreina Baj, Pietro Giorgio Spezia, Daniele Focosi, Cristian Zago, Alberto Colombo, Gianluca Cassani, Renee Pasciuta, Antonio Tamborini, Agostino Rossi, Martina Prestia, Riccardo Capuano, Lorenzo Azzi, Annalisa Donadini, Giuseppe Catanoso, Paolo Antonio Grossi, Lorenzo Maffioli, Gianni Bonelli

Abstract
We report an imported case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant P.1 detected in an asymptomatic traveler who arrived in Italy on an indirect flight from Brazil. This case shows the risk for introduction of SARS-CoV-2 variants from indirect flights and the need for continued SARS-CoV-2 surveillance.

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09/02/2021 Articles
Evidence for SARS-CoV-2 related coronaviruses circulating in bats and ...

Evidence for SARS-CoV-2 related coronaviruses circulating in bats and pangolins in Southeast Asia

NATURE

Authors
Supaporn Wacharapluesadee, Chee Wah Tan, Patarapol Maneeorn, Prateep Duengkae, Feng Zhu, Yutthana Joyjinda, Thongchai Kaewpom, Wan Ni Chia, Weenassarin Ampoot, Beng Lee Lim, Kanthita Worachotsueptrakun, Vivian Chih-Wei Chen, Nutthinee Sirichan, Chanida Ruchisrisarod, Apaporn Rodpan, Kirana Noradechanon, Thanawadee Phaichana, Niran Jantarat, Boonchu Thongnumchaima, Changchun Tu, Gary Crameri, Martha M. Stokes, Thiravat Hemachudha, Lin-Fa Wang

Abstract
Among the many questions unanswered for the COVID-19 pandemic are the origin of SARS-CoV-2 and the potential role of intermediate animal host(s) in the early animal-to-human transmission. The discovery of RaTG13 bat coronavirus in China suggested a high probability of a bat origin. Here we report molecular and serological evidence of SARS-CoV-2 related coronaviruses (SC2r-CoVs) actively circulating in bats in Southeast Asia. Whole genome sequences were obtained from five independent bats (Rhinolophus acuminatus) in a Thai cave yielding a single isolate (named RacCS203) which is most related to the RmYN02 isolate found in Rhinolophus malayanus in Yunnan, China. SARS-CoV-2 neutralizing antibodies were also detected in bats of the same colony and in a pangolin at a wildlife checkpoint in Southern Thailand. Antisera raised against the receptor binding domain (RBD) of RmYN02 was able to cross-neutralize SARS-CoV-2 despite the fact that the RBD of RacCS203 or RmYN02 failed to bind ACE2. Although the origin of the virus remains unresolved, our study extended the geographic distribution of genetically diverse SC2r-CoVs from Japan and China to Thailand over a 4800-km range. Cross-border surveillance is urgently needed to find the immediate progenitor virus of SARS-CoV-2.

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08/02/2021 Articles
Biomechanical Characterization of SARS-CoV-2 Spike RBD and Human ACE2 ...

Biomechanical Characterization of SARS-CoV-2 Spike RBD and Human ACE2 Protein-Protein Interaction

BIOPHYSICAL JOURNAL

Authors
Wenpeng Cao, Chuqiao Dong, Seonghan Kim, Decheng Hou, Wanbo Tai, Lanying Du, Wonpil Im, X. Frank Zhang

ABSTRACT
The current COVID-19 pandemic has led to a devastating impact across the world.
SARS-CoV-2 (the virus causing COVID-19) is known to use the receptor-binding domain
(RBD) at viral surface spike (S) protein to interact with the angiotensin-converting enzyme 2
(ACE2) receptor expressed on many human cell types. The RBD−ACE2 interaction is a crucial
step to mediate the host cell entry of SARS-CoV-2. Recent studies indicate that the ACE2
interaction with the SARS-CoV-2 S protein has a higher affinity than its binding with the
structurally identical S protein of SARS-CoV-1, the virus causing the 2002-2004 SARS
outbreak. However, the biophysical mechanism behind such binding affinity difference is
unclear. This study utilizes combined single-molecule force spectroscopy and steered molecular
dynamics (SMD) simulation approaches to quantify the specific interactions between CoV-2 or
CoV-1 RBD and ACE2. Depending on the loading rates, the unbinding forces between CoV-2
RBD and ACE2 range from 70 to 105 pN and are 30-40% higher than those of CoV-1 RBD and
ACE2 under similar loading rates. SMD results indicate that CoV-2 RBD interacts with the Nlinked glycan on Asn90 of ACE2. This interaction is mostly absent in the CoV-1 RBD−ACE2
complex. During the SMD simulations, the extra RBD-N-glycan interaction contributes to a
greater force and prolonged interaction lifetime. The observation is confirmed by our
experimental force spectroscopy study. After removing N-linked glycans on ACE2, its
mechanical binding strength with CoV-2 RBD decreases to a similar level of the CoV-1
RBD−ACE2 interaction. Together, the study uncovers the mechanism behind the difference in
ACE2 binding between SARS-CoV-2 and SARS-CoV-1 and could help develop new strategies
to block SARS-CoV-2 entry

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05/02/2021 Articles
SARS-CoV-2 evolution during treatment of chronic infection

NATURE

Authors
Steven A. Kemp, Dami A. Collier, Rawlings P. Datir, Isabella A. T. M. Ferreira, Salma Gayed, Aminu Jahun, Myra Hosmillo, Chloe Rees-Spear, Petra Mlcochova, Ines Ushiro Lumb, David J. Roberts, Anita Chandra, Nigel Temperton, The CITIID-NIHR BioResource COVID-19 Collaboration, The COVID-19 Genomics UK (COG-UK) Consortium, Katherine Sharrocks, Elizabeth Blane, Yorgo Modis, Kendra Leigh, John Briggs, Marit van Gils, Kenneth G. C. Smith, John R. Bradley, Chris Smith, Rainer Doffinger, Lourdes Ceron-Gutierrez, Gabriela Barcenas-Morales, David D. Pollock, Richard A. Goldstein, Anna Smielewska, Jordan P. Skittrall, Theodore Gouliouris, Ian G. Goodfellow, Effrossyni Gkrania-Klotsas, Christopher J. R. Illingworth, Laura E. McCoy, Ravindra K. Gupta

Abstract
SARS-CoV-2 Spike protein is critical for virus infection via engagement of ACE21, and is a major antibody target. Here we report chronic SARS-CoV-2 with reduced sensitivity to neutralising antibodies in an immune suppressed individual treated with convalescent plasma, generating whole genome ultradeep sequences over 23 time points spanning 101 days. Little change was observed in the overall viral population structure following two courses of remdesivir over the first 57 days. However, following convalescent plasma therapy we observed large, dynamic virus population shifts, with the emergence of a dominant viral strain bearing D796H in S2 and ΔH69/ΔV70 in the S1 N-terminal domain NTD of the Spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype diminished in frequency, before returning during a final, unsuccessful course of convalescent plasma. In vitro, the Spike escape double mutant bearing ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, whilst maintaining infectivity similar to wild type. D796H appeared to be the main contributor to decreased susceptibility but incurred an infectivity defect. The ΔH69/ΔV70 single mutant had two-fold higher infectivity compared to wild type, possibly compensating for the reduced infectivity of D796H. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy associated with emergence of viral variants with evidence of reduced susceptibility to neutralising antibodies.

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04/02/2021 Articles
CryoDRGN: reconstruction of heterogeneous cryo-EM structures using neu...

CryoDRGN: reconstruction of heterogeneous cryo-EM structures using neural networks

BIORXIV

Authors
Ellen D. Zhong, Tristan Bepler, Bonnie Berger, Joseph H. Davis

Abstract
Cryo-electron microscopy (cryo-EM) single-particle analysis has proven powerful in determining the structures of rigid macromolecules. However, many imaged protein complexes exhibit conformational and compositional heterogeneity that poses a major challenge to existing three-dimensional reconstruction methods. Here, we present cryoDRGN, an algorithm that leverages the representation power of deep neural networks to directly reconstruct continuous distributions of 3D density maps and map per-particle heterogeneity of single-particle cryo-EM datasets. Using cryoDRGN, we uncovered residual heterogeneity in high-resolution datasets of the 80S ribosome and the RAG complex, revealed a new structural state of the assembling 50S ribosome, and visualized large-scale continuous motions of a spliceosome complex. CryoDRGN contains interactive tools to visualize a dataset’s distribution of per-particle variability, generate density maps for exploratory analysis, extract particle subsets for use with other tools and generate trajectories to visualize molecular motions. CryoDRGN is open-source software freely available at http://cryodrgn.csail.mit.edu.

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03/02/2021 News
Scientists call for fully open sharing of coronavirus genome data

NATURE

Authors
Richard Van Noorden

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02/02/2021 Articles
What's Going On With All These Coronavirus Variants? An Illustrated Gu...

What's Going On With All These Coronavirus Variants? An Illustrated Guide

NPR

Authors
MICHAELEEN DOUCLEFF, MEREDITH RIZZO

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02/02/2021 Articles
The effect of the D614G substitution on the structure of the spike gly...

The effect of the D614G substitution on the structure of the spike glycoprotein of SARS-CoV-2

PNAS

Authors
Donald J. Benton, Antoni G. Wrobel, Chloë Roustan, Annabel Borg, Pengqi Xu, Stephen R. Martin, Peter B. Rosenthal, John J. Skehel, Steven J. Gamblin

Abstract
The majority of currently circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses have mutant spike glycoproteins that contain the D614G substitution. Several studies have suggested that spikes with this substitution are associated with higher virus infectivity. We use cryo-electron microscopy to compare G614 and D614 spikes and show that the G614 mutant spike adopts a range of more open conformations that may facilitate binding to the SARS-CoV-2 receptor, ACE2, and the subsequent structural rearrangements required for viral membrane fusion.

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29/01/2021 PERSPECTIVE
Insights from SARS-CoV-2 sequences

SCIENCE

Authors
Michael A. Martin, David VanInsberghe, Katia Koelle

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29/01/2021 Articles
Genomic monitoring of SARS-CoV-2 uncovers an Nsp1 deletion variant tha...

Genomic monitoring of SARS-CoV-2 uncovers an Nsp1 deletion variant that modulates type I interferon response

CELL

Authors
Jing-wen Lin, Chao Tang, Han-cheng Wei, Baowen Du, Chuan Chen, Minjin Wang, Yongzhao Zhou, Ming-xia Yu, Lu Cheng, Suvi Kuivanen, Natacha S. Ogando, Lev Levanov, Yuancun Zhao, Chang-ling Li, Ran Zhou, Zhidan Li, Yiming Zhang, Ke Sun, Chengdi Wang, Li Chen, Xia Xiao, Xiuran Zheng, Sha-sha Chen, Zhen Zhou, Ruirui Yang, Dan Zhang, Mengying Xu, Junwei Song, Danrui Wang, Yupeng Li, ShiKun Lei, Wanqin Zeng, Qingxin Yang, Ping He, Yaoyao Zhang, Lifang Zhou, Ling Cao, Feng Luo, Huayi Liu, Liping Wang, Fei Ye, Ming Zhang, Mengjiao Li, Wei Fan, Xinqiong Li, Kaiju Li, Bowen Ke, Jiannan Xu, Huiping Yang, Shusen He, Ming Pan, Yichen Yan, Yi Zha, Lingyu Jiang, Changxiu Yu, Yingfen Liu, Zhiyong Xu, Qingfeng Li, Yongmei Jiang, Jiufeng Sun, Wei Hong, Hongping Wei, Guangwen Lu, Olli Vapalahti, Yunzi Luo, Yuquan Wei, Thomas Connor, Wenjie Tan, Eric J. Snijder, Teemu Smura, Weimin Li, Jia Geng, Binwu Ying, Lu Chen

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29/01/2021 News
Nota técnica aborda Sars-CoV-2 e nova variante no AM

FIOCRUZ (FUNDACAO OSVALDO CRUZ)

Authors
Fiocruz Amazônia

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29/01/2021 News
Covid-19: Sore throat, fatigue, and myalgia are more common with new U...

Covid-19: Sore throat, fatigue, and myalgia are more common with new UK variant

THE BMJ

Authors
Elisabeth Mahase

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28/01/2021 Articles
Circulating SARS-CoV-2 spike N439K variants maintain fitness while eva...

Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity

CELL

Authors
Emma C. Thomson, Laura E. Rosen, James G. Shepherd, Roberto Spreafico, Ana da Silva Filipe, Jason A. Wojcechowskyj, Chris Davis, Luca Piccoli, David J. Pascall, Josh Dillen, Spyros Lytras, Nadine Czudnochowski, Rajiv Shah, Marcel Meury, Natasha Jesudason, Anna De Marco, Kathy Li, Jessica Bassi, Aine O’Toole, Dora Pinto, Rachel M. Colquhoun, Katja Culap, Ben Jackson, Fabrizia Zatta, Andrew Rambaut, Stefano Jaconi, Vattipally B. Sreenu, Jay Nix, Ivy Zhang, Ruth F. Jarrett, William G. Glass, Martina Beltramello, Kyriaki Nomikou, Matteo Pizzuto, Lily Tong, Elisabetta Cameroni, Tristan I. Croll, Natasha Johnson, Julia Di Iulio, Arthur Wickenhagen, Alessandro Ceschi, Aoife M. Harbison, Daniel Mair, Paolo Ferrari, Katherine Smollett, Federica Sallusto, Stephen Carmichael, Christian Garzoni, Jenna Nichols, Massimo Galli, Joseph Hughes, Agostino Riva, Antonia Ho, Marco Schiuma, Malcolm G. Semple, Peter J.M. Openshaw, Elisa Fadda, J. Kenneth Baillie, John D. Chodera, The ISARIC4C Investigators, the COVID-19 Genomics UK (COG-UK) consortium, Suzannah J. Rihn, Samantha J. Lycett, Herbert W. Virgin, Amalio Telenti, Davide Corti, David L. Robertson, Gyorgy Snell

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26/01/2021 News
Covid-19: New UK variant may be linked to increased death rate, early ...

Covid-19: New UK variant may be linked to increased death rate, early data indicate

THE BMJ

Authors
Gareth Iacobucci

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25/01/2021 Report
Prospective mapping of viral mutations that escape antibodies used to ...

Prospective mapping of viral mutations that escape antibodies used to treat COVID-19

SCIENCE

Authors
Tyler N. Starr, Allison J. Greaney, Amin Addetia, William W. Hannon, Manish C. Choudhary, Adam S. Dingens, Jonathan Z. Li, Jesse D. Bloom

Abstract
Antibodies are a potential therapy for SARS-CoV-2, but the risk of the virus evolving to escape them remains unclear. Here we map how all mutations to SARS-CoV-2’s receptor-binding domain (RBD) affect binding by the antibodies in the REGN-COV2 cocktail and the antibody LY-CoV016. These complete maps uncover a single amino-acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2, as well as during in vitro viral escape selections. Finally, the maps reveal that mutations escaping the individual antibodies are already present in circulating SARS-CoV-2 strains. Overall, these complete escape maps enable interpretation of the consequences of mutations observed during viral surveillance.

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25/01/2021 Case Report
Prospective mapping of viral mutations that escape antibodies used to ...

Prospective mapping of viral mutations that escape antibodies used to treat COVID-19

SCIENCE

Authors
Tyler N. Starr, Allison J. Greaney, Amin Addetia, William W. Hannon, Manish C. Choudhary, Adam S. Dingens, Jonathan Z. Li, Jesse D. Bloom

Abstract
Antibodies are a potential therapy for SARS-CoV-2, but the risk of the virus evolving to escape them remains unclear. Here we map how all mutations to SARS-CoV-2’s receptor-binding domain (RBD) affect binding by the antibodies in the REGN-COV2 cocktail and the antibody LY-CoV016. These complete maps uncover a single amino-acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2, as well as during in vitro viral escape selections. Finally, the maps reveal that mutations escaping the individual antibodies are already present in circulating SARS-CoV-2 strains. Overall, these complete escape maps enable interpretation of the consequences of mutations observed during viral surveillance.

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18/01/2021 News
Covid-19: What new variants are emerging and how are they being invest...

Covid-19: What new variants are emerging and how are they being investigated?

THE BMJ

Authors
Elisabeth Mahase

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15/01/2021 Articles
New coronavirus variants could cause more reinfections, require update...

New coronavirus variants could cause more reinfections, require updated vaccines

SCIENCE

Authors
Kai Kupferschmidt

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15/01/2021 Report
Learning the language of viral evolution and escape

SCIENCE

Authors
Brian Hie, Ellen D. Zhong, Bonnie Berger, Bryan Bryson

Abstract
The ability for viruses to mutate and evade the human immune system and cause infection, called viral escape, remains an obstacle to antiviral and vaccine development. Understanding the complex rules that govern escape could inform therapeutic design. We modeled viral escape with machine learning algorithms originally developed for human natural language. We identified escape mutations as those that preserve viral infectivity but cause a virus to look different to the immune system, akin to word changes that preserve a sentence’s grammaticality but change its meaning. With this approach, language models of influenza hemagglutinin, HIV-1 envelope glycoprotein (HIV Env), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike viral proteins can accurately predict structural escape patterns using sequence data alone. Our study represents a promising conceptual bridge between natural language and viral evolution.

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15/01/2021 Press Release
Emergence of SARS-CoV-2 B.1.1.7 Lineage — United States, December 29, ...

Emergence of SARS-CoV-2 B.1.1.7 Lineage — United States, December 29, 2020–January 12, 2021

MMWR (MORBIDITY AND MORTALITY WEEKLY REPORT)

Authors
Summer E. Galloway, Prabasaj Paul, Duncan R. MacCannell, Michael A. Johansson, John T. Brooks, Adam MacNeil, Rachel B. Slayton, Suxiang Tong, Benjamin J. Silk, Gregory L. Armstrong, Matthew Biggerstaff, Vivien G. Dugan

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12/01/2021 Correspondence
First detection of SARS-CoV-2 spike protein N501 mutation in Italy in ...

First detection of SARS-CoV-2 spike protein N501 mutation in Italy in August, 2020

THE LANCET

Authors
Simona Fiorentini, Serena Messali, Alberto Zani, Francesca Caccuri, Marta Giovanetti, Massimo Ciccozzi, Arnaldo Caruso

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08/01/2021 PERSPECTIVE
SARS-CoV-2 spillover events

SCIENCE

Authors
Peng Zhou, Zheng-Li Shi

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08/01/2021 Research
Establishment and lineage dynamics of the SARS-CoV-2 epidemic in the U...

Establishment and lineage dynamics of the SARS-CoV-2 epidemic in the UK

SCIENCE

Authors
Louis du Plessis, John T. McCrone, Alexander E. Zarebski, Verity Hill, Christopher Ruis, Bernardo Gutierrez, Jayna Raghwani, Jordan Ashworth, Rachel Colquhoun, Thomas R. Connor, Nuno R. Faria, Ben Jackson, Nicholas J. Loman, Áine O’Toole, Samuel M. Nicholls, Kris V. Parag, Emily Scher, Tetyana I. Vasylyeva, Erik M. Volz, Alexander Watts, Isaac I. Bogoch, Kamran Khan, David M. Aanensen, Moritz U. G. Kraemer, Andrew Rambaut, Oliver G. Pybus

Abstract
The UK’s COVID-19 epidemic during early 2020 was one of world’s largest and unusually well represented by virus genomic sampling. Here we reveal the fine-scale genetic lineage structure of this epidemic through analysis of 50,887 SARS-CoV-2 genomes, including 26,181 from the UK sampled throughout the country’s first wave of infection. Using large-scale phylogenetic analyses, combined with epidemiological and travel data, we quantify the size, spatio-temporal origins and persistence of genetically-distinct UK transmission lineages. Rapid fluctuations in virus importation rates resulted in >1000 lineages; those introduced prior to national lockdown tended to be larger and more dispersed. Lineage importation and regional lineage diversity declined after lockdown, while lineage elimination was size-dependent. We discuss the implications of our genetic perspective on transmission dynamics for COVID-19 epidemiology and control.

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05/01/2021 Articles
New variant of SARS-CoV-2 in UK causes surge of COVID-19

THE LANCET

Authors
Tony Kirby

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31/12/2020 Articles
Estimated transmissibility and severity of novel SARS-CoV-2 Variant of...

Estimated transmissibility and severity of novel SARS-CoV-2 Variant of Concern 202012/01 in England

CMMID REPOSITORY

Authors
Nicholas Davies, Rosanna C Barnard, Christopher I Jarvis, Adam J Kucharski, James D Munday, Carl A.B. Pearson, Timothy W Russell, Damien C Tully, Sam Abbott, Amy Gimma, William Waites, Kerry LM Wong, Kevin van Zandvoort, Rosalind M Eggo, Sebastian Funk, Mark Jit, Katherine E Atkins, W John Edmunds

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29/12/2020 Risk Assestment
Risk related to spread of new SARS- CoV-2 variants of concern in the E...

Risk related to spread of new SARS- CoV-2 variants of concern in the EU/EEA

ECDC

Authors
EUROPEAN CENTRE FOR DISEASE PREVENTION AND CONTROL

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22/12/2020 Articles
Phylogenetic supertree reveals detailed evolution of SARS‐CoV‐2

NATURE

Authors
Tingting Li, Dongxia Liu, Yadi Yang, Jiali Guo, Yujie Feng, Xinmo Zhang, Shilong Cheng, Jie Feng

Abstract
Corona Virus Disease 2019 (COVID-19) caused by the emerged coronavirus SARS-CoV-2 is spreading globally. The origin of SARS-Cov-2 and its evolutionary relationship is still ambiguous. Several reports attempted to figure out this critical issue by genome-based phylogenetic analysis, yet limited progress was obtained, principally owing to the disability of these methods to reasonably integrate phylogenetic information from all genes of SARS-CoV-2. Supertree method based on multiple trees can produce the overall reasonable phylogenetic tree. However, the supertree method has been barely used for phylogenetic analysis of viruses. Here we applied the matrix representation with parsimony (MRP) pseudo-sequence supertree analysis to study the origin and evolution of SARS-CoV-2. Compared with other phylogenetic analysis methods, the supertree method showed more resolution power for phylogenetic analysis of coronaviruses. In particular, the MRP pseudo-sequence supertree analysis firmly disputes bat coronavirus RaTG13 be the last common ancestor of SARS-CoV-2, which was implied by other phylogenetic tree analysis based on viral genome sequences. Furthermore, the discovery of evolution and mutation in SARS-CoV-2 was achieved by MRP pseudo-sequence supertree analysis. Taken together, the MRP pseudo-sequence supertree provided more information on the SARS-CoV-2 evolution inference relative to the normal phylogenetic tree based on full-length genomic sequences.

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22/12/2020 Articles
Emergence and rapid spread of a new severe acute respiratory syndrome-...

Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa

MEDRXIV

Authors
Houriiyah Tegally, Eduan Wilkinson, Marta Giovanetti, Arash Iranzadeh, Vagner Fonseca, Jennifer Giandhari, Deelan Doolabh, Sureshnee Pillay, Emmanuel James San, Nokukhanya Msomi, Koleka Mlisana, Anne von Gottberg, Sibongile Walaza, Mushal Allam, Arshad Ismail, Thabo Mohale, Allison J Glass, Susan Engelbrecht, Gert Van Zyl, Wolfgang Preiser, Francesco Petruccione, Alex Sigal, Diana Hardie, Gert Marais, Marvin Hsiao, Stephen Korsman, Mary-Ann Davies, Lynn Tyers, Innocent Mudau, Denis York, Caroline Maslo, Dominique Goedhals, Shareef Abrahams, Oluwakemi Laguda-Akingba, Arghavan Alisoltani-Dehkordi, Adam Godzik, Constantinos Kurt Wibmer, Bryan Trevor Sewell, José Lourenço, Luiz Carlos Junior Alcantara, Sergei L Kosakovsky Pond, Steven Weaver, Darren Martin, Richard J Lessells, Jinal N Bhiman, Carolyn Williamson, Tulio de Oliveira

Summary
Continued uncontrolled transmission of the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in many parts of the world is creating the conditions for significant virus evolution. Here, we describe a new SARS-CoV-2 lineage (501Y.V2) characterised by eight lineage-defining mutations in the spike protein, including three at important residues in the receptor-binding domain (K417N, E484K and N501Y) that may have functional significance. This lineage emerged in South Africa after the first epidemic wave in a severely affected metropolitan area, Nelson Mandela Bay, located on the coast of the Eastern Cape Province. This lineage spread rapidly, becoming within weeks the dominant lineage in the Eastern Cape and Western Cape Provinces. Whilst the full significance of the mutations is yet to be determined, the genomic data, showing the rapid displacement of other lineages, suggest that this lineage may be associated with increased transmissibility.

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21/12/2020 Articles
Genomic epidemiology reveals multiple introductions of SARS-CoV-2 from...

Genomic epidemiology reveals multiple introductions of SARS-CoV-2 from mainland Europe into Scotland

NATURE

Authors
Ana da Silva Filipe, James G. Shepherd, Thomas Williams, Joseph Hughes, Elihu Aranday-Cortes, Patawee Asamaphan, Shirin Ashraf, Carlos Balcazar, Kirstyn Brunker, Alasdair Campbell, Stephen Carmichael, Chris Davis, Rebecca Dewar, Michael D. Gallagher, Rory Gunson, Verity Hill, Antonia Ho, Ben Jackson, Edward James, Natasha Jesudason, Natasha Johnson, E. Carol McWilliam Leitch, Kathy Li, Alasdair MacLean, Daniel Mair, David A. McAllister, John T. McCrone, Sarah E. McDonald, Martin P. McHugh, A. Keith Morris, Jenna Nichols, Marc Niebel, Kyriaki Nomikou, Richard J. Orton, Áine O’Toole, Massimo Palmarini, Benjamin J. Parcell, Yasmin A. Parr, Andrew Rambaut, Stefan Rooke, Sharif Shaaban, Rajiv Shah, Joshua B. Singer, Katherine Smollett, Igor Starinskij, Lily Tong, Vattipally B. Sreenu, Elizabeth Wastnedge, The COVID-19 Genomics UK (COG-UK) Consortium, Matthew T. G. Holden, David L. Robertson, Kate Templeton, Emma C. Thomson

Abstract
Coronavirus disease 2019 (COVID-19) was first diagnosed in Scotland on 1 March 2020. During the first month of the outbreak, 2,641 cases of COVID-19 led to 1,832 hospital admissions, 207 intensive care admissions and 126 deaths. We aimed to identify the source and number of introductions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into Scotland using a combined phylogenetic and epidemiological approach. Sequencing of 1,314 SARS-CoV-2 viral genomes from available patient samples enabled us to estimate that SARS-CoV-2 was introduced to Scotland on at least 283 occasions during February and March 2020. Epidemiological analysis confirmed that early introductions of SARS-CoV-2 originated from mainland Europe (the majority from Italy and Spain). We identified subsequent early outbreaks in the community, within healthcare facilities and at an international conference. Community transmission occurred after 2 March, 3 weeks before control measures were introduced. Earlier travel restrictions or quarantine measures, both locally and internationally, would have reduced the number of COVID-19 cases in Scotland. The risk of multiple reintroduction events in future waves of infection remains high in the absence of population immunity.

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21/12/2020 Research
Emergence of a Highly Fit SARS-CoV-2 Variant

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Ralph S. Baric, Elizabeth G. Phimister

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19/12/2020 Case Report
Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage...

Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations

ARAMBAUT

Authors
Andrew Rambaut, Nick Loman, Oliver Pybus, Wendy Barclay, Jeff Barrett, Alesandro Carabelli, Tom Connor, Tom Peacock, David L Robertson, Erik Volz

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18/12/2020 Research
Susceptibility of Domestic Swine to Experimental Infection with Severe...

Susceptibility of Domestic Swine to Experimental Infection with Severe Acute Respiratory Syndrome Coronavirus 2

CDC (CENTERS FOR DISEASE CONTROL AND PREVENTION)

Authors
Brad S. Pickering, Greg Smith, Mathieu M. Pinette, Carissa Embury-Hyatt, Estella Moffat, Peter Marszal, Charles E. Lewis

Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent that causes coronavirus disease, has been shown to infect several species. The role of domestic livestock and associated risks for humans in close contact with food production animals remains unknown for many species. Determining the susceptibility of pigs to SARS-CoV-2 is critical to a One Health approach to manage potential risk for zoonotic transmission. We found that pigs are susceptible to SARS-CoV-2 after oronasal inoculation. Among 16 animals, we detected viral RNA in group oral fluids and in nasal wash from 2 pigs, but live virus was isolated from only 1 pig. Antibodies also were detected in only 2 animals at 11 and 13 days postinoculation but were detected in oral fluid samples at 6 days postinoculation, indicating antibody secretion. These data highlight the need for additional livestock assessment to determine the potential role of domestic animals in the SARS-CoV-2 pandemic.

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16/12/2020 News
Covid-19: New coronavirus variant is identified in UK

THE BMJ

Authors
Jacqui Wise

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04/12/2020 Articles
Evidence of exposure to SARS-CoV-2 in cats and dogs from households in...

Evidence of exposure to SARS-CoV-2 in cats and dogs from households in Italy

NATURE

Authors
E. I. Patterson , G. Elia, A. Grassi, A. Giordano, C. Desario, M. Medardo, S. L. Smith, E. R. Anderson1 , T. Prince7, G. T. Patterson 6, E. Lorusso2, M. S. Lucente2, G. Lanave2, S. Lauzi, U. Bonfanti, A. Stranieri, V. Martella, F. Solari Basano, V. R. Barrs, A. D. Radford, U. Agrimi, G. L. Hughes, S. Paltrinieri, N. Decaro

Abstract
SARS-CoV-2 emerged from animals and is now easily transmitted between people. Sporadic detection of natural cases in animals alongside successful experimental infections of pets, such as cats, ferrets and dogs, raises questions about the susceptibility of animals under natural conditions of pet ownership. Here, we report a large-scale study to assess SARS-CoV-2 infection in 919 companion animals living in northern Italy, sampled at a time of frequent human infection. No animals tested PCR positive. However, 3.3% of dogs and 5.8% of cats had measurable SARS-CoV-2 neutralizing antibody titers, with dogs from COVID-19 positive households being significantly more likely to test positive than those from COVID-19 negative households. Understanding risk factors associated with this and their potential to infect other species requires urgent investigation.

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19/11/2020 Articles
SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of vi...

SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis

THE LANCET

Authors
Muge Cevik, Matthew Tate, Ollie Lloyd, Alberto Enrico Maraolo, Jenna Schafers, Antonia Ho

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18/11/2020 News
What the data say about asymptomatic COVID infections

NATURE

Authors
Bianca Nogrady

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12/11/2020 Report
SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and tr...

SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo

SCIENCE

Authors
Yixuan J. Hou, Shiho Chiba, Peter Halfmann, Camille Ehre, Makoto Kuroda, Kenneth H. Dinnon III, Sarah R. Leist, Alexandra Schäfer, Noriko Nakajima, Kenta Takahashi, Rhianna E. Lee, Teresa M. Mascenik, Rachel Graham, Caitlin E. Edwards, Longping V. Tse, Kenichi Okuda, Alena J. Markmann, Luther Bartelt, Aravinda de Silva, David M. Margolis, Richard C. Boucher, Scott H. Randell, Tadaki Suzuki, Lisa E. Gralinski, Yoshihiro Kawaoka, Ralph S. Baric

Abstract
The spike D614G substitution is prevalent in global SARS-CoV-2 strains, but its effects on viral pathogenesis and transmissibility remain unclear. We engineered a SARS-CoV-2 variant containing this substitution. The variant exhibits more efficient infection, replication, and competitive fitness in primary human airway epithelial cells, but maintains similar morphology and in vitro neutralization properties, compared with the ancestral wild-type virus. Infection of human angiotensin-converting enzyme 2 (ACE2) transgenic mice and Syrian hamsters with both viruses resulted in similar viral titers in respiratory tissues and pulmonary disease. However, the D614G variant transmits significantly faster and displayed increased competitive fitness than the wild-type virus in hamsters. These data show that the D614G substitution enhances SARS-CoV-2 infectivity, competitive fitness, and transmission in primary human cells and animal models.

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30/10/2020 PERSPECTIVE
Will SARS- CoV-2 become endemic?

SCIENCE

Authors
Jeffrey Shaman, Marta Galanti

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28/10/2020 Research
Escape from neutralizing antibodies by SARS-CoV-2 spike protein varian...

Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants

ELIFE

Authors
Yiska Weisblum, Fabian Schmidt, Fengwen Zhang, Justin DaSilva, Daniel Poston, Julio CC Lorenzi, Frauke Muecksch, Magdalena Rutkowska, Hans-Heinrich Hoffmann, Eleftherios Michailidis, Christian Gaebler, Marianna Agudelo, Alice Cho, Zijun Wang, Anna Gazumyan, Melissa Cipolla, Larry Luchsinger, Christopher D Hillyer, Marina Caskey, Davide F Robbiani, Charles M Rice, Michel C Nussenzweig, Theodora Hatziioannou, Paul D Bieniasz

Abstract
Neutralizing antibodies elicited by prior infection or vaccination are likely to be key for future protection of individuals and populations against SARS-CoV-2. Moreover, passively administered antibodies are among the most promising therapeutic and prophylactic anti-SARS-CoV-2 agents. However, the degree to which SARS-CoV-2 will adapt to evade neutralizing antibodies is unclear. Using a recombinant chimeric VSV/SARS-CoV-2 reporter virus, we show that functional SARS-CoV-2 S protein variants with mutations in the receptor-binding domain (RBD) and N-terminal domain that confer resistance to monoclonal antibodies or convalescent plasma can be readily selected. Notably, SARS-CoV-2 S variants that resist commonly elicited neutralizing antibodies are now present at low frequencies in circulating SARS-CoV-2 populations. Finally, the emergence of antibody-resistant SARS-CoV-2 variants that might limit the therapeutic usefulness of monoclonal antibodies can be mitigated by the use of antibody combinations that target distinct neutralizing epitopes.

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27/10/2020 Articles
Structural basis for potent neutralization of SARS-CoV-2 and role of a...

Structural basis for potent neutralization of SARS-CoV-2 and role of antibody affinity maturation

NATURE

Authors
Nicholas K. Hurlburt, Emilie Seydoux, Yu-Hsin Wan, Venkata Viswanadh Edara, Andrew B. Stuart, Junli Feng, Mehul S. Suthar, Andrew T. McGuire, Leonidas Stamatatos, Marie Pancera

Abstract
SARS-CoV-2 is a betacoronavirus virus responsible for the COVID-19 pandemic. Here, we determine the X-ray crystal structure of a potent neutralizing monoclonal antibody, CV30, isolated from a patient infected with SARS-CoV-2, in complex with the receptor binding domain. The structure reveals that CV30 binds to an epitope that overlaps with the human ACE2 receptor binding motif providing a structural basis for its neutralization. CV30 also induces shedding of the S1 subunit, indicating an additional mechanism of neutralization. A germline reversion of CV30 results in a substantial reduction in both binding affinity and neutralization potential indicating the minimal somatic mutation is needed for potently neutralizing antibodies against SARS-CoV-2.

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27/10/2020 STUDY PROTOCOL
Coronavirus disease 2019 (COVID-19)

THE BMJ

Authors
Nicholas J. Beeching, Tom E. Fletcher, Robert Fowler, William A. Petri, Xin Zhang, Ran Nir-Paz

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26/10/2020 Articles
Spike mutation D614G alters SARS-CoV-2 fitness

NATURE

Authors
Jessica A. Plante, Yang Liu, Jianying Liu, Hongjie Xia, Bryan A. Johnson, Kumari G. Lokugamage, Xianwen Zhang, Antonio E. Muruato, Jing Zou, Camila R. Fontes-Garfias, Divya Mirchandani, Dionna Scharton, John P. Bilello, Zhiqiang Ku, Zhiqiang An, Birte Kalveram, Alexander N. Freiberg, Vineet D. Menachery, Xuping Xie, Kenneth S. Plante, Scott C. Weaver & Pei-Yong Shi

Abstract
A spike protein mutation D614G became dominant in SARS-CoV-2 during the COVID-19 pandemic1,2. However, the impact on viral spread and vaccine efficacy remains to be defined. Here, we engineer the D614G mutation in the USA-WA1/2020 strain and characterize its effect. D614G enhances replication on human lung epithelial cells and primary human airway tissues through an improved infectivity of virions. Hamsters infected with the G614 variant produced higher infectious titers in the nasal washes and trachea, but not lungs, confirming clinical evidence that the D614G mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increases transmission. Sera from D614-infected hamsters exhibit modestly higher neutralization titers against G614 virus than against D614 virus, indicating that (i) the mutation may not reduce the ability of vaccines in clinical trials to protect against COVID-19 and (ii) therapeutic antibodies should be tested against the circulating G614 virus. Together with clinical findings, our work underscores the importance of this mutation in viral spread, vaccine efficacy, and antibody therapy.

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23/10/2020 Analysis
Virology, transmission, and pathogenesis of SARS-CoV-2

THE BMJ

Authors
Muge Cevik, Krutika Kuppalli, Jason Kindrachuk, Malik Peiris

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07/10/2020 Research
The effect of temperature on persistence of SARS-CoV-2 on common surfa...

The effect of temperature on persistence of SARS-CoV-2 on common surfaces

BMC

Authors
Shane Riddell, Sarah Goldie, Andrew Hill, Debbie Eagles, Trevor W. Drew

Abstract
Background
The rate at which COVID-19 has spread throughout the globe has been alarming. While the role of fomite transmission is not yet fully understood, precise data on the environmental stability of SARS-CoV-2 is required to determine the risks of fomite transmission from contaminated surfaces.

Methods
This study measured the survival rates of infectious SARS-CoV-2, suspended in a standard ASTM E2197 matrix, on several common surface types. All experiments were carried out in the dark, to negate any effects of UV light. Inoculated surfaces were incubated at 20 °C, 30 °C and 40 °C and sampled at various time points.

Results
Survival rates of SARS-CoV-2 were determined at different temperatures and D-values, Z-values and half-life were calculated. We obtained half lives of between 1.7 and 2.7 days at 20 °C, reducing to a few hours when temperature was elevated to 40 °C. With initial viral loads broadly equivalent to the highest titres excreted by infectious patients, viable virus was isolated for up to 28 days at 20 °C from common surfaces such as glass, stainless steel and both paper and polymer banknotes. Conversely, infectious virus survived less than 24 h at 40 °C on some surfaces.

Conclusion
These findings demonstrate SARS-CoV-2 can remain infectious for significantly longer time periods than generally considered possible. These results could be used to inform improved risk mitigation procedures to prevent the fomite spread of COVID-19.

Read More »

29/09/2020 Articles
Viral epitope profiling of COVID-19 patients reveals cross-reactivity ...

Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity

SCIENCE

Authors
Ellen Shrock, Eric Fujimura, Tomasz Kula, Richard T. Timms, I-Hsiu Lee4, Yumei Leng, Matthew L. Robinson5, Brandon M. Sie, Mamie Z. Li, Yuezhou Chen, Jennifer Logue, Adam Zuiani, Denise McCulloch, Felipe J. N. Lelis, Stephanie Henson, Daniel R. Monaco, Meghan Travers, Shaghayegh Habibi, William A. Clarke, Patrizio Caturegli, Oliver Laeyendecker, Alicja Piechocka-Trocha, Jon Li, Ashok Khatri, Helen Y. Chu6, MGH COVID-19 Collection & Processing Team, Alexandra-Chloé Villani, Kyle Kays, Marcia B. Goldberg, Nir Hacohen, Michael R. Filbin, Xu G. Yu, Bruce D. Walker, Duane R. Wesemann, H. Benjamin Larman, James A. Lederer, Stephen J. Elledge

Abstract
Understanding humoral responses to SARS-CoV-2 is critical for improving diagnostics, therapeutics, and vaccines. Deep serological profiling of 232 COVID-19 patients and 190 pre-COVID-19 era controls using VirScan revealed over 800 epitopes in the SARS-CoV-2 proteome, including 10 epitopes likely recognized by neutralizing antibodies. Pre-existing antibodies in controls recognized SARS-CoV-2 ORF1, while only COVID-19 patients primarily recognized spike and nucleoprotein. A machine learning model trained on VirScan data predicted SARS-CoV-2 exposure history with 99% sensitivity and 98% specificity; a rapid Luminex-based diagnostic was developed from the most discriminatory SARS-CoV-2 peptides. Individuals with more severe COVID-19 exhibited stronger and broader SARS-CoV-2 responses, weaker antibody responses to prior infections, and higher incidence of CMV and HSV-1, possibly influenced by demographic covariates. Among hospitalized patients, males make greater SARS-CoV-2 antibody responses than females.

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29/09/2020 Articles
High-resolution structures ofthe SARS-CoV-2 2′-O- methyltransferase re...

High-resolution structures ofthe SARS-CoV-2 2′-O- methyltransferase reveal strategies for structure-based inhibitor design

SCIENCE

Authors
Monica Rosas-Lemus, George Minasov, Ludmilla Shuvalova, Nicole L. Inniss, Olga Kiryukhina, Joseph Brunzelle, Karla J. F. Satchell

Abstract
There are currently no antiviral therapies specific for SARS-CoV-2, the virus responsible for the global pandemic disease COVID-19. To facilitate structure-based drug design, we conducted an x-ray crystallographic study of the SARS-CoV-2 nsp16-nsp10 2′-O-methyltransferase complex, which methylates Cap-0 viral mRNAs to improve viral protein translation and to avoid host immune detection. We determined the structures for nsp16-nsp10 heterodimers bound to the methyl donor S-adenosylmethionine (SAM), the reaction product S-adenosylhomocysteine (SAH), or the SAH analog sinefungin (SFG). We also solved structures for nsp16-nsp10 in complex with the methylated Cap-0 analog m7GpppA and either SAM or SAH. Comparative analyses between these structures and published structures for nsp16 from other betacoronaviruses revealed flexible loops in open and closed conformations at the m7GpppA-binding pocket. Bound sulfates in several of the structures suggested the location of the ribonucleic acid backbone phosphates in the ribonucleotide-binding groove. Additional nucleotide-binding sites were found on the face of the protein opposite the active site. These various sites and the conserved dimer interface could be exploited for the development of antiviral inhibitors.

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24/09/2020 Articles
COVID19: an announced pandemic

NATURE

Authors
Sara Platto, Tongtong Xue, Ernesto Carafoli

Abstract
A severe upper respiratory tract syndrome caused by the new coronavirus has now spread to the entire world as a highly contagious pandemic. The large scale explosion of the disease is conventionally traced back to January of this year in the Chinese province of Hubei, the wet markets of the principal city of Wuhan being assumed to have been the specific causative locus of the sudden explosion of the infection. A number of findings that are now coming to light show that this interpretation of the origin and history of the pandemic is overly simplified. A number of variants of the coronavirus would in principle have had the ability to initiate the pandemic well before January of this year. However, even if the COVID-19 had become, so to say, ready, conditions in the local environment would have had to prevail to induce the loss of the biodiversity’s “dilution effect” that kept the virus under control, favoring its spillover from its bat reservoir to the human target. In the absence of these appropriate conditions only abortive attempts to initiate the pandemic could possibly occur: a number of them did indeed occur in China, and probably elsewhere as well. These conditions were unfortunately present at the wet marked in Wuhan at the end of last year.

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21/09/2020 Articles
COVID-19 image classification using deep features and fractional-order...

COVID-19 image classification using deep features and fractional-order marine predators algorithm

NATURE

Authors
Ahmed T. Sahlol, Dalia Yousri, Ahmed A. Ewees, Mohammed A. A. Al-qaness, Robertas Damasevicius, Mohamed Abd Elaziz

Abstract
Currently, we witness the severe spread of the pandemic of the new Corona virus, COVID-19, which causes dangerous symptoms to humans and animals, its complications may lead to death. Although convolutional neural networks (CNNs) is considered the current state-of-the-art image classification technique, it needs massive computational cost for deployment and training. In this paper, we propose an improved hybrid classification approach for COVID-19 images by combining the strengths of CNNs (using a powerful architecture called Inception) to extract features and a swarm-based feature selection algorithm (Marine Predators Algorithm) to select the most relevant features. A combination of fractional-order and marine predators algorithm (FO-MPA) is considered an integration among a robust tool in mathematics named fractional-order calculus (FO). The proposed approach was evaluated on two public COVID-19 X-ray datasets which achieves both high performance and reduction of computational complexity. The two datasets consist of X-ray COVID-19 images by international Cardiothoracic radiologist, researchers and others published on Kaggle. The proposed approach selected successfully 130 and 86 out of 51 K features extracted by inception from dataset 1 and dataset 2, while improving classification accuracy at the same time. The results are the best achieved on these datasets when compared to a set of recent feature selection algorithms. By achieving 98.7%, 98.2% and 99.6%, 99% of classification accuracy and F-Score for dataset 1 and dataset 2, respectively, the proposed approach outperforms several CNNs and all recent works on COVID-19 images.

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17/09/2020 Articles
Receptor binding and priming of the spike protein of SARS-CoV-2 for me...

Receptor binding and priming of the spike protein of SARS-CoV-2 for membrane fusion

NATURE

Authors
Donald J. Benton, Antoni G. Wrobel, Pengqi Xu, Chloë Roustan, Stephen R. Martin, Peter B. Rosenthal, John J. Skehel, Steven J. Gamblin

Abstract
SARS-CoV-2 infection is initiated by virus binding to ACE2 cell surface receptors1–4, followed by fusion of virus and cell membranes to release the virus genome into the cell. Both receptor binding and membrane fusion activities are mediated by the virus Spike glycoprotein, S5–7. As with other class I membrane fusion proteins, S is post-translationally cleaved, in this case by furin, into S1 and S2 components that remain associated following cleavage8–10. Fusion activation following receptor binding is proposed to involve the exposure of a second proteolytic site (S2’), cleavage of which is required for the fusion peptide release11,12. We have investigated the binding of ACE2 to the furin-cleaved form of SARS-CoV-2 S by cryoEM. We classify ten different molecular species including the unbound, closed spike trimer, the fully open ACE2-bound trimer, and dissociated monomeric S1 bound to ACE2. The ten structures describe ACE2 binding events which destabilise the spike trimer, progressively opening up, and out, the individual S1 components. The opening process reduces S1 contacts and un-shields the trimeric S2 core, priming fusion activation and dissociation of ACE2-bound S1 monomers. The structures also reveal refolding of an S1 subdomain following ACE2 binding, that disrupts interactions with S2, notably involving Asp61413–15, leading to destabilisation of the structure of S2 proximal to the secondary (S2’) cleavage site.

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11/09/2020 PERSPECTIVE
Coronavirus dons a new crown

SCIENCE

Authors
Nuruddin Unchwaniwala, Paul Ahlquist

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11/09/2020 Report
A molecular pore spans the double membrane of the coronavirus replicat...

A molecular pore spans the double membrane of the coronavirus replication organelle

SCIENCE

Authors
Georg Wolff, Ronald W. A. L. Limpens, Jessika C. Zevenhoven-Dobbe, Ulrike Laugks, Shawn Zheng, Anja W. M. de Jong, Roman I. Koning, David A. Agard, Kay Grünewald, Abraham J. Koster, Eric J. Snijder, Montserrat Bárcena1

Abstract
Coronavirus genome replication is associated with virus-induced cytosolic double-membrane vesicles, which may provide a tailored microenvironment for viral RNA synthesis in the infected cell. However, it is unclear how newly synthesized genomes and messenger RNAs can travel from these sealed replication compartments to the cytosol to ensure their translation and the assembly of progeny virions. In this study, we used cellular cryo–electron microscopy to visualize a molecular pore complex that spans both membranes of the double-membrane vesicle and would allow export of RNA to the cytosol. A hexameric assembly of a large viral transmembrane protein was found to form the core of the crown-shaped complex. This coronavirus-specific structure likely plays a key role in coronavirus replication and thus constitutes a potential drug target.

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11/09/2020 Articles
Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2...

Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor

NATURE

Authors
Jinsung Yang, Simon J. L. Petitjean, Melanie Koehler, Qingrong Zhang, Andra C. Dumitru, Wenzhang Chen, Sylvie Derclaye, Stéphane P. Vincent, Patrice Soumillion, David Alsteens

Study of the interactions established between the viral glycoproteins and their host receptors is of critical importance for a better understanding of virus entry into cells. The novel coronavirus SARS-CoV-2 entry into host cells is mediated by its spike glycoprotein (S-glycoprotein), and the angiotensin-converting enzyme 2 (ACE2) has been identified as a cellular receptor. Here, we use atomic force microscopy to investigate the mechanisms by which the S-glycoprotein binds to the ACE2 receptor. We demonstrate, both on model surfaces and on living cells, that the receptor binding domain (RBD) serves as the binding interface within the S-glycoprotein with the ACE2 receptor and extract the kinetic and thermodynamic properties of this binding pocket. Altogether, these results provide a picture of the established interaction on living cells. Finally, we test several binding inhibitor peptides targeting the virus early attachment stages, offering new perspectives in the treatment of the SARS-CoV-2 infection.

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03/09/2020 Original Research
Profiling and characterization of SARS-CoV-2 mutants’ infectivity and ...

Profiling and characterization of SARS-CoV-2 mutants’ infectivity and antigenicity

NATURE

Authors
Lin Wang, Ling Wang, Hui Zhuang

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03/09/2020 PERSPECTIVE
On Becoming a Plague Doctor

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Mark Earnest

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02/09/2020 Articles
Ocular conjunctival inoculation of SARS-CoV-2 can cause mild COVID-19 ...

Ocular conjunctival inoculation of SARS-CoV-2 can cause mild COVID-19 in rhesus macaques

NATURE

Authors
Wei Deng, Linlin Bao, Hong Gao, Zhiguang Xiang, Yajin Qu, Zhiqi Song, Shuran Gong, Jiayi Liu, Jiangning Liu, Pin Yu, Feifei Qi, Yanfeng Xu, Fengli Li, Chong Xiao, Qi Lv, Jing Xue, Qiang Wei, Mingya Liu, Guanpeng Wang, Shunyi Wang, Haisheng Yu, Ting Chen, Xing Liu, Wenjie Zhao, Yunlin Han, Chuan Qin

ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmitted through the respiratory route, but potential extra-respiratory routes of SARS-CoV-2 transmission remain uncertain. Here we inoculated five rhesus macaques with 1 × 106 TCID50 of SARS-CoV-2 conjunctivally (CJ), intratracheally (IT), and intragastrically (IG). Nasal and throat swabs collected from CJ and IT had detectable viral RNA at 1–7 days post-inoculation (dpi). Viral RNA was detected in anal swabs from only the IT group at 1–7 dpi. Viral RNA was undetectable in tested swabs and tissues after intragastric inoculation. The CJ infected animal had a higher viral load in the nasolacrimal system than the IT infected animal but also showed mild interstitial pneumonia, suggesting distinct virus distributions. This study shows that infection via the conjunctival route is possible in non-human primates; further studies are necessary to compare the relative risk and pathogenesis of infection through these different routes in more detail.

24/08/2020 Articles
Emerging of a SARS-CoV-2 viral strain with a deletion in nsp1

RESEARCH SQUARE

Authors
Francesca Benedetti Greg Snyder Marta Giovanetti Silvia Angeletti Massimo Ciccozzi Davide Zella


ABSTRACT
Background:
The new Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was first detected in Wuhan (China) in December of 2019 is responsible for the current global pandemic.
Phylogenetic analysis revealed that it is similar to other betacoronaviruses, such as SARS-CoV and Middle-Eastern Respiratory Syndrome, MERS-CoV. Its genome is ∼30 kb in length and contains two large overlapping polyproteins, ORF1a and ORF1ab that encode for several structural and non-structural proteins. The non-structural protein 1 (nsp1) is arguably the most important pathogenic determinant, and previous studies on SARS-CoV indicate that it is both involved in viral replication and hampering the innate immune system response. Detailed experiments of site-specific mutagenesis and in vitro reconstitution studies determined that the mechanisms of action are mediated by i) the presence of specific amino acid residues of nsp1 and b) the interaction between the protein and the host’s small ribosomal unit. In fact, substitution of certain amino acids resulted in reduction of its negative effects.
Methods: A total of 17928 genome sequences were obtained from the GISAID database (December 2019 to July 2020) from patients infected by SARS-CoV-2 from different areas around the world. Genomes alignment was performed using MAFFT (REFF) and the nsp1 genomic regions were identified using BioEdit and verified using BLAST. Nsp1 protein of SARS-CoV-2 with and without deletion have been subsequently modelled using I-TASSER.
Results: We identified SARS-CoV-2 genome sequences, from several Countries, carrying a previously unknown deletion of 9 nucleotides in position 686-694, corresponding to the AA position 241-243 (KSF). This deletion was found in different geographical areas. Structural prediction modelling suggests an effect on the C-terminal tail structure.
Conclusions: Modelling analysis of a newly identified deletion of 3 amino acids (KSF) of SARS-CoV-2 nsp1 suggests that this deletion could affect the structure of the C-terminal region of the protein, important for regulation of viral replication and negative effect on host’s gene expression. In addition, substitution of the two amino acids (KS) from nsp1 of SARS-CoV was previously reported to revert loss of interferon-alpha expression. The deletion that we describe indicates that SARS-CoV-2 is undergoing profound genomic changes. It is important to: i) confirm the spreading of this particular viral strain, and potentially of strains with other deletions in the nsp1 protein, both in the population of asymptomatic and pauci-symptomatic subjects, and ii) correlate these changes in nsp1 with potential decreased viral pathogenicity.

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23/08/2020 Reviews
Prospect of SARS-CoV-2 spike protein: Potential role in vaccine and th...

Prospect of SARS-CoV-2 spike protein: Potential role in vaccine and therapeutic development

ELSEVIER

Authors
Subodh Kumar, Samrata Anil, M.Tharappela, Zhong Lia, Hongmin Liab


ABSTRACT
The recent outbreak of the betacoronavirus SARS-CoV-2 has become a significant concern to public health care worldwide. As of August 19, 2020, more than 22,140,472 people are infected, and over 781,135 people have died due to this deadly virus. In the USA alone, over 5,482,602 people are currently infected, and more than 171,823 people have died. SARS-CoV-2 has shown a higher infectivity rate and a more extended incubation period as compared to previous coronaviruses. SARS-CoV-2 binds much more strongly than SARS-CoV to the same host receptor, angiotensin-converting enzyme 2 (ACE2). Previously, several methods to develop a vaccine against SARS-CoV or MERS-CoV have been tried with limited success. Since SARS-CoV-2 uses the spike (S) protein for entry to the host cell, it is one of the most preferred targets for making vaccines or therapeutics against SARS-CoV-2. In this review, we have summarised the characteristics of the S protein, as well as the different approaches being used for the development of vaccines and/or therapeutics based on the S protein.

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20/08/2020 NEWSDESK
The origin of SARS-CoV-2

THE LANCET

Authors
Talha Burki


ABSTRACT
The recent outbreak of the betacoronavirus SARS-CoV-2 has become a significant concern to public health care worldwide. As of August 19, 2020, more than 22,140,472 people are infected, and over 781,135 people have died due to this deadly virus. In the USA alone, over 5,482,602 people are currently infected, and more than 171,823 people have died. SARS-CoV-2 has shown a higher infectivity rate and a more extended incubation period as compared to previous coronaviruses. SARS-CoV-2 binds much more strongly than SARS-CoV to the same host receptor, angiotensin-converting enzyme 2 (ACE2). Previously, several methods to develop a vaccine against SARS-CoV or MERS-CoV have been tried with limited success. Since SARS-CoV-2 uses the spike (S) protein for entry to the host cell, it is one of the most preferred targets for making vaccines or therapeutics against SARS-CoV-2. In this review, we have summarised the characteristics of the S protein, as well as the different approaches being used for the development of vaccines and/or therapeutics based on the S protein.

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18/08/2020 Letter
Peripheral immunophenotypes in children with multisystem inflammatory ...

Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection

NATURE

Authors
Michael J. Carter, Matthew Fish, Aislinn Jennings, Katie J. Doores, Paul Wellman, Jeffrey Seow, Sam Acors, Carl Graham, Emma Timms, Julia Kenny, Stuart Neil, Michael H. Malim, Shane M. Tibby, Manu Shankar-Hari


ABSTRACT
Recent reports highlight a new clinical syndrome in children related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1—multisystem inflammatory syndrome in children (MIS-C)—which comprises multiorgan dysfunction and systemic inflammation2,3,4,5,6,7,8,9,10,11,12,13. We performed peripheral leukocyte phenotyping in 25 children with MIS-C, in the acute (n = 23; worst illness within 72 h of admission), resolution (n = 14; clinical improvement) and convalescent (n = 10; first outpatient visit) phases of the illness and used samples from seven age-matched healthy controls for comparisons. Among the MIS-C cohort, 17 (68%) children were SARS-CoV-2 seropositive, suggesting previous SARS-CoV-2 infections14,15, and these children had more severe disease. In the acute phase of MIS-C, we observed high levels of interleukin-1β (IL-1β), IL-6, IL-8, IL-10, IL-17, interferon-γ and differential T and B cell subset lymphopenia. High CD64 expression on neutrophils and monocytes, and high HLA-DR expression on γδ and CD4+CCR7+ T cells in the acute phase, suggested that these immune cell populations were activated. Antigen-presenting cells had low HLA-DR and CD86 expression, potentially indicative of impaired antigen presentation. These features normalized over the resolution and convalescence phases. Overall, MIS-C presents as an immunopathogenic illness1 and appears distinct from Kawasaki disease.

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18/08/2020 Research
Haplotype networks of SARS-CoV-2 infections in the Diamond Princess cr...

Haplotype networks of SARS-CoV-2 infections in the Diamond Princess cruise ship outbreak

PNAS

Authors
Tsuyoshi Sekizuka, Kentaro Itokawa, Tsutomu Kageyama, Shinji Saito, Ikuyo Takayama, Hideki Asanuma, Naganori Nao, Rina Tanaka, Masanori Hashino, View ORCID ProfileTakuri Takahashi, Hajime Kamiya, View ORCID ProfileTakuya Yamagishi, View ORCID ProfileKensaku Kakimoto, Motoi Suzuki, Hideki Hasegawa, Takaji Wakita, Makoto Kuroda


ABSTRACT
The Diamond Princess cruise ship was put under quarantine offshore Yokohama, Japan, after a passenger who disembarked in Hong Kong was confirmed as a coronavirus disease 2019 case. We performed whole-genome sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly from PCR+ clinical specimens and conducted a phylogenetic analysis of the outbreak. All tested isolates exhibited a transversion at G11083T, suggesting that SARS-CoV-2 dissemination on the Diamond Princess originated from a single introduction event before the quarantine started. Although further spreading might have been prevented by quarantine, some progeny clusters could be linked to transmission through mass-gathering events in the recreational areas and direct transmission among passengers who shared cabins during the quarantine. This study demonstrates the usefulness of haplotype network/phylogeny analysis in identifying potential infection routes. In late December 2019, an outbreak of a novel coronavirus disease 2019 (COVID-19) originated in Wuhan, China. It was caused by a new strain of betacoronavirus: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (1, 2). The Diamond Princess (DP) cruise ship was put under quarantine soon after its return to Yokohama, Japan on February 3, 2020, after visiting Kagoshima, Hong Kong, Vietnam, Taiwan, and Okinawa, because an 80-y-old passenger who disembarked in Hong Kong was confirmed as a COVID-19 case on February 1 after the ship had departed from Hong Kong on January 25. The passenger presented with a cough beginning on January 23. From February 3 to 4 the health status of all passengers and crew members was investigated by quarantine officers and upper-respiratory specimens were collected from symptomatic passengers, crew, and their close contacts for SARS-CoV-2 PCR testing. As of February 5, there were a total of 3,711 individuals with 2,666 passengers and 1,045 crew members on board the DP. The Japanese government asked about 3,600 passengers and crew members to stay on board in Yokohama during the 14-d isolation period through February 19 to prevent the further spread of COVID-19 cases. A field epidemiological study about the DP COVID-19 cases has been published (3). As of March 8, 697 COVID-19 cases had been identified among the 3,711 persons on the DP and 7 people had died (4). Here, we have generated a haplotype network of the SARS-CoV-2 outbreak using genome-wide single nucleotide variations (SNVs), identifying the genotypes of isolates that disseminated in the DP cruise ship after quarantine on February 5, 2020.

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18/08/2020 Articles
Effects of a major deletion in the SARS-CoV-2 genome on the severity o...

Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study

THE LANCET

Authors
Barnaby E Young, Siew-Wai Fong, Yi-Hao Chan, Tze-Minn Mak, Li Wei Ang, Danielle E Anderson, Cheryl Yi-Pin Lee, Siti Naqiah Amrun, Bernett Lee, Yun Shan Goh, Yvonne C F Su, Wycliffe E Wei, Shirin Kalimuddin, Louis Yi Ann Chai, Surinder Pada, Seow Yen Tan, Louisa Sun, Purnima Parthasarathy, Yuan Yi Constance Chen, Timothy Barkham, Raymond Tzer Pin Lin, Sebastian Maurer-Stroh, Yee-Sin Leo, Lin-Fa Wang, Laurent Renia, Vernon J Lee, Gavin J D Smith, David Chien Lye, Lisa F P Ng

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16/08/2020 Reviews
Biological fluid dynamics of airborne COVID-19 infection

SPRINGER LINK

Authors
Giovanni Seminara, Bruno Carli, Guido Forni, Sandro Fuzzi, Andrea Mazzino, Andrea Rinaldo

Abstract
We review the state of knowledge on the bio-fluid dynamic mechanisms involved in the transmission of the infection from SARS-CoV-2. The relevance of the subject stems from the key role of airborne virus transmission by viral particles released by an infected person via coughing, sneezing, speaking or simply breathing. Speech droplets generated by asymptomatic disease carriers are also considered for their viral load and potential for infection. Proper understanding of the mechanics of the complex processes whereby the two-phase flow emitted by an infected individual disperses into the environment would allow us to infer from first principles the practical rules to be imposed on social distancing and on the use of facial and eye protection, which to date have been adopted on a rather empirical basis. These measures need compelling scientific validation. A deeper understanding of the relevant biological fluid dynamics would also allow us to evaluate the contrasting effects of natural or forced ventilation of environments on the transmission of contagion: the risk decreases as the viral load is diluted by mixing effects but contagion is potentially allowed to reach larger distances from the infected source. To that end, our survey supports the view that a formal assessment of a number of open problems is needed. They are outlined in the discussion.

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13/08/2020 Editorial
A dangerous rush for vaccines

SCIENCE

Authors
H. Holden Thorp

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31/07/2020 PERSPECTIVE
How does SARS-CoV-2 cause COVID-19?

SCIENCE

Authors
Nicholas J. Matheson, Paul J. Lehner



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30/07/2020 Articles
Differential Tropism of SARS-CoV and SARS-CoV-2 in Bat Cells

CENTERS FOR DISEASE CONTROL AND PREVENTION

Authors
Susanna K.P. Lau1Comments to Author , Antonio C.P. Wong1, Hayes K.H. Luk1, Kenneth S.M. Li, Joshua Fung, Zirong He, Flora K.K. Cheng, Tony T.Y. Chan, Stella Chu, Kam Leng Aw-Yong, Terrence C.K. Lau, Kitty S.C. Fung, Patrick C.Y. Woo

Abstract
Severe acute respiratory syndrome coronavirus 2 did not replicate efficiently in 13 bat cell lines, whereas severe acute respiratory syndrome coronavirus replicated efficiently in kidney cells of its ancestral host, the Rhinolophus sinicus bat, suggesting different evolutionary origins. Structural modeling showed that RBD/RsACE2 binding may contribute to the differential cellular tropism.

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24/07/2020 Articles
Structural basis of RNA cap modification by SARS-CoV-2

NATURE

Authors
Thiruselvam Viswanathan, Shailee Arya, Siu-Hong Chan, Shan Qi, Nan Dai, Anurag Misra, Jun-Gyu Park, Fatai Oladunni, Dmytro Kovalskyy, Robert A. Hromas, Luis Martinez-Sobrido, Yogesh K. Gupta



ABSTRACT
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19 illness, has caused millions of infections worldwide. In SARS coronaviruses, the non-structural protein 16 (nsp16), in conjunction with nsp10, methylates the 5′-end of virally encoded mRNAs to mimic cellular mRNAs, thus protecting the virus from host innate immune restriction. We report here the high-resolution structure of a ternary complex of SARS-CoV-2 nsp16 and nsp10 in the presence of cognate RNA substrate analogue and methyl donor, S-adenosyl methionine (SAM). The nsp16/nsp10 heterodimer is captured in the act of 2′-O methylation of the ribose sugar of the first nucleotide of SARS-CoV-2 mRNA. We observe large conformational changes associated with substrate binding as the enzyme transitions from a binary to a ternary state. This induced fit model provides mechanistic insights into the 2′-O methylation of the viral mRNA cap. We also discover a distant (25 Å) ligand-binding site unique to SARS-CoV-2, which can alternatively be targeted, in addition to RNA cap and SAM pockets, for antiviral development.

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24/07/2020 Communication
Presence of Genetic Variants Among Young Men With Severe COVID-19

JAMA

Authors
Caspar I. van der Made, Annet Simons, Janneke Schuurs-Hoeijmakers, Guus van den Heuvel, Tuomo Mantere, Simone Kersten, Rosanne C. van Deuren, Marloes Steehouwer, Simon V. van Reijmersdal, Martin Jaeger Tom Hofste, Galuh Astuti, Jordi Corominas Galbany, Vyne van der Schoot, Hans van der Hoeven, Wanda Hagmolen, Eva Klijn, Catrien van den Meer, Jeroen Fiddelaers, Quirijn de Mast, Chantal P. Bleeker-Rovers, Leo A. B. Joosten, Helger G. Yntema, Christian Gilissen, Marcel Nelen, Jos W. M. van der Meer, Han G. Brunner, Mihai G. Netea, Frank L. van de Veerdonk, Alexander Hoischen



ABSTRACT
Importance Severe coronavirus disease 2019 (COVID-19) can occur in younger, predominantly male, patients without preexisting medical conditions. Some individuals may have primary immunodeficiencies that predispose to severe infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Objective To explore the presence of genetic variants associated with primary immunodeficiencies among young patients with COVID-19.
Design, Setting, and Participants Case series of pairs of brothers without medical history meeting the selection criteria of young (age <35 years) brother pairs admitted to the intensive care unit (ICU) due to severe COVID-19. Four men from 2 unrelated families were admitted to the ICUs of 4 hospitals in the Netherlands between March 23 and April 12, 2020. The final date of follow-up was May 16, 2020. Available family members were included for genetic variant segregation analysis and as controls for functional experiments.
Exposure Severe COVID-19.
Main Outcome and Measures Results of rapid clinical whole-exome sequencing, performed to identify a potential monogenic cause. Subsequently, basic genetic and immunological tests were performed in primary immune cells isolated from the patients and family members to characterize any immune defects.
Results The 4 male patients had a mean age of 26 years (range, 21-32), with no history of major chronic disease. They were previously well before developing respiratory insufficiency due to severe COVID-19, requiring mechanical ventilation in the ICU. The mean duration of ventilatory support was 10 days (range, 9-11); the mean duration of ICU stay was 13 days (range, 10-16). One patient died. Rapid clinical whole-exome sequencing of the patients and segregation in available family members identified loss-of-function variants of the X-chromosomal TLR7. In members of family 1, a maternally inherited 4-nucleotide deletion was identified (c.2129_2132del; p.[Gln710Argfs*18]); the affected members of family 2 carried a missense variant (c.2383G>T; p.[Val795Phe]). In primary peripheral blood mononuclear cells from the patients, downstream type I interferon (IFN) signaling was transcriptionally downregulated, as measured by significantly decreased mRNA expression of IRF7, IFNB1, and ISG15 on stimulation with the TLR7 agonist imiquimod as compared with family members and controls. The production of IFN-γ, a type II IFN, was decreased in patients in response to stimulation with imiquimod.
Conclusions and Relevance In this case series of 4 young male patients with severe COVID-19, rare putative loss-of-function variants of X-chromosomal TLR7 were identified that were associated with impaired type I and II IFN responses. These preliminary findings provide insights into the pathogenesis of COVID-19.

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24/07/2020 Viewpoint
Particle sizes of infectious aerosols: implications for infection cont...

Particle sizes of infectious aerosols: implications for infection control

THE LANCET

Authors
Kevin P Fennelly



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23/07/2020 Communication
HLA-B*44 and C*01 Prevalence Correlates with Covid19 Spreading across ...

HLA-B*44 and C*01 Prevalence Correlates with Covid19 Spreading across Italy

MDPI

Authors
Pierpaolo Correale, Luciano Mutti, Francesca Pentimalli, Giovanni Baglio, Rita Emilena Saladino,Pierpaolo Sileri, Antonio Giordano



ABSTRACT
The spread of COVID-19 is showing huge, unexplained, differences between northern and southern Italy. We hypothesized that the regional prevalence of specific class I human leukocyte antigen (HLA) alleles, which shape the anti-viral immune response, might partly underlie these differences. Through an ecological approach, we analyzed whether a set of HLA alleles (A, B, C), known to be involved in the immune response against infections, correlates with COVID-19 incidence. COVID-19 data were provided by the National Civil Protection Department, whereas HLA allele prevalence was retrieved through the Italian Bone-Marrow Donors Registry. Among all the alleles, HLA-A*25, B*08, B*44, B*15:01, B*51, C*01, and C*03 showed a positive log-linear correlation with COVID-19 incidence rate fixed on 9 April 2020 in proximity of the national outbreak peak (Pearson’s coefficients between 0.50 and 0.70, p-value < 0.0001), whereas HLA-B*14, B*18, and B*49 showed an inverse log-linear correlation (Pearson’s coefficients between −0.47 and −0.59, p-value < 0.0001). When alleles were examined simultaneously using a multiple regression model to control for confounding factors, HLA-B*44 and C*01 were still positively and independently associated with COVID-19: a growth rate of 16% (95%CI: 0.1–35%) per 1% point increase in B*44 prevalence; and of 19% (95%CI: 1–41%) per 1% point increase in C*01 prevalence. Our epidemiologic analysis, despite the limits of the ecological approach, is strongly suggestive of a permissive role of HLA-C*01 and B*44 towards SARS-CoV-2 infection, which warrants further investigation in case-control studies. This study opens a new potential avenue for the identification of sub-populations at risk, which could provide Health Services with a tool to define more targeted clinical management strategies and priorities in vaccination campaigns.

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23/07/2020 Report
Structure-based design of prefusion-stabilized SARS-CoV-2 spikes

SCIENCE

Authors
Ching-Lin Hsieh, Jory A. Goldsmith, Jeffrey M. Schaub, Andrea M. DiVenere, Hung-Che Kuo, Kamyab Javanmardi, Kevin C. Le, Daniel Wrapp, Alison G. Lee, Yutong Liu, Chia-Wei Chou, Patrick O. Byrne, Christy K. Hjorth, Nicole V. Johnson, John Ludes-Meyers, Annalee W. Nguyen, Juyeon Park, Nianshuang Wang, Dzifa Amengor, Jason J. Lavinder, Gregory C. Ippolito, Jennifer A. Maynard2, Ilya J. Finkelstein, Jason S. McLellan



ABSTRACT
The COVID-19 pandemic has led to accelerated efforts to develop therapeutics and vaccines. A key target of these efforts is the spike (S) protein, which is metastable and difficult to produce recombinantly. Here, we characterized 100 structure-guided spike designs and identified 26 individual substitutions that increased protein yields and stability. Testing combinations of beneficial substitutions resulted in the identification of HexaPro, a variant with six beneficial proline substitutions exhibiting ~10-fold higher expression than its parental construct and the ability to withstand heat stress, storage at room temperature, and three freeze-thaw cycles. A 3.2 Å-resolution cryo-EM structure of HexaPro confirmed that it retains the prefusion spike conformation. High-yield production of a stabilized prefusion spike protein will accelerate the development of vaccines and serological diagnostics for SARS-CoV-2.

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22/07/2020 Articles
Potent neutralizing antibodies directed to multiple epitopes on SARS-C...

Potent neutralizing antibodies directed to multiple epitopes on SARS-CoV-2 spike

NATURE

Authors
Lihong Liu, Pengfei Wang, Manoj S. Nair, Jian Yu, Micah Rapp, Qian Wang, Yang Luo, Jasper F-W. Chan, Vincent Sahi, Amir Figueroa, Xinzheng V. Guo, Gabriele Cerutti, Jude Bimela, Jason Gorman, Tongqing Zhou, Zhiwei Chen, Kwok-Yung Yuen, Peter D. Kwong, Joseph G. Sodroski, Michael T. Yin, Zizhang Sheng, Yaoxing Huang, Lawrence Shapiro, David D. Ho



ABSTRACT
The SARS-CoV-2 pandemic rages on with devasting consequences on human lives and the global economy1,2. The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this novel coronavirus. Here we report the isolation of 61 SARS-CoV-2-neutralizing monoclonal antibodies from 5 infected patients hospitalized with severe disease. Among these are 19 antibodies that potently neutralized the authentic SARS-CoV-2 in vitro, 9 of which exhibited exquisite potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng/mL. Epitope mapping showed this collection of 19 antibodies to be about equally divided between those directed to the receptor-binding domain (RBD) and those to the N-terminal domain (NTD), indicating that both of these regions at the top of the viral spike are immunogenic. In addition, two other powerful neutralizing antibodies recognized quaternary epitopes that overlap with the domains at the top of the spike. Cryo-electron microscopy reconstructions of one antibody targeting RBD, a second targeting NTD, and a third bridging two separate RBDs revealed recognition of the closed, “all RBD-down” conformation of the spike. Several of these monoclonal antibodies are promising candidates for clinical development as potential therapeutic and/or prophylactic agents against SARS-CoV-2.

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21/07/2020 Articles
Discovery and Genomic Characterization of a 382-Nucleotide Deletion in...

Discovery and Genomic Characterization of a 382-Nucleotide Deletion in ORF7b and ORF8 during the Early Evolution of SARS-CoV-2

ASM JOURNALS

Authors
Yvonne C. F. Su, Danielle E. Anderson, Barnaby E. Young, Martin Linster, Feng Zhu, Jayanthi Jayakumar, Yan Zhuang, Shirin Kalimuddin, Jenny G. H. Low, Chee Wah Tan, Wan Ni Chia, Tze Minn Mak, Sophie Octavia, Jean-Marc Chavatte, Raphael T. C. Lee, Surinder Pada, Seow Yen Tan, Louisa Sun, Gabriel Z. Yan, Sebastian Maurer-Stroh, Ian H. Mendenhall, Yee-Sin Leo, David Chien Lye, Lin-Fa Wang, Gavin J. D. Smith



ABSTRACT
To date, limited genetic changes in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome have been described. Here, we report a 382-nucleotide (nt) deletion in SARS-CoV-2 that truncates open reading frame 7b (ORF7b) and ORF8, removing the ORF8 transcription regulatory sequence (TRS) and eliminating ORF8 transcription. The earliest 382-nt deletion variant was detected in Singapore on 29 January 2020, with the deletion viruses circulating in the country and accounting for 23.6% (45/191) of SARS-CoV-2 samples screened in this study. SARS-CoV-2 with the same deletion has since been detected in Taiwan, and other ORF7b/8 deletions of various lengths, ranging from 62 nt to 345 nt, have been observed in other geographic locations, including Australia, Bangladesh, and Spain. Mutations or deletions in ORF8 of SARS-CoV have been associated with reduced replicative fitness and virus attenuation. In contrast, the SARS-CoV-2 382-nt deletion viruses showed significantly higher replicative fitness in vitro than the wild type, while no difference was observed in patient viral load, indicating that the deletion variant viruses retained their replicative fitness. A robust antibody response to ORF8 has been observed in SARS-CoV-2 infection, suggesting that the emergence of ORF8 deletions may be due to immune-driven selection and that further deletion variants may emerge during the sustained transmission of SARS-CoV-2 in humans.

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17/07/2020 Articles
ACE2 gene variants may underlie interindividual variability and suscep...

ACE2 gene variants may underlie interindividual variability and susceptibility to COVID-19 in the Italian population

NATURE

Authors
Elisa Benetti, Rossella Tita, Ottavia Spiga, Andrea Ciolfi, Giovanni Birolo, Alessandro Bruselles, Gabriella Doddato, Annarita Giliberti, Caterina Marconi, Francesco Musacchia, Tommaso Pippucci, Annalaura Torella, Alfonso Trezza, Floriana Valentino, Margherita Baldassarri, Alfredo Brusco, Rosanna Asselta, Mirella Bruttini, Simone Furini, Marco Seri, Vincenzo Nigro, Giuseppe Matullo, Marco Tartaglia, Francesca Mari, GEN-COVID Multicenter Study, Alessandra Renieri & Anna Maria Pinto



ABSTRACT
In December 2019, an initial cluster of interstitial bilateral pneumonia emerged in Wuhan, China. A human-to-human transmission was assumed and a previously unrecognized entity, termed coronavirus disease-19 (COVID-19) due to a novel coronavirus (SARS-CoV-2) was described. The infection has rapidly spread out all over the world and Italy has been the first European country experiencing the endemic wave with unexpected clinical severity in comparison with Asian countries. It has been shown that SARS-CoV-2 utilizes angiotensin converting enzyme 2 (ACE2) as host receptor and host proteases for cell surface binding and internalization. Thus, a predisposing genetic background can give reason for interindividual disease susceptibility and/or severity. Taking advantage of the Network of Italian Genomes (NIG), here we mined whole-exome sequencing data of 6930 Italian control individuals from five different centers looking for ACE2 variants. A number of variants with a potential impact on protein stability were identified. Among these, three more common missense changes, p.(Asn720Asp), p.(Lys26Arg), and p.(Gly211Arg) were predicted to interfere with protein structure and stabilization. Rare variants likely interfering with the internalization process, namely p.(Leu351Val) and p.(Pro389His), predicted to interfere with SARS-CoV-2 spike protein binding, were also observed. Comparison of ACE2 WES data between a cohort of 131 patients and 258 controls allowed identifying a statistically significant (P value < 0.029) higher allelic variability in controls compared with patients. These findings suggest that a predisposing genetic background may contribute to the observed interindividual clinical variability associated with COVID-19, allowing an evidence-based risk assessment leading to personalized preventive measures and therapeutic options.

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10/07/2020 Reviews
Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus...

Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19)

JAMA

Authors
W. Joost Wiersinga, Andrew Rhodes, Allen C. Cheng, Sharon J. Peacock, Hallie C. Prescott



ABSTRACT
Importance The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19. Observations SARS-CoV-2 is spread primarily via respiratory droplets during close face-to-face contact. Infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. The average time from exposure to symptom onset is 5 days, and 97.5% of people who develop symptoms do so within 11.5 days. The most common symptoms are fever, dry cough, and shortness of breath. Radiographic and laboratory abnormalities, such as lymphopenia and elevated lactate dehydrogenase, are common, but nonspecific. Diagnosis is made by detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing, although false-negative test results may occur in up to 20% to 67% of patients; however, this is dependent on the quality and timing of testing. Manifestations of COVID-19 include asymptomatic carriers and fulminant disease characterized by sepsis and acute respiratory failure. Approximately 5% of patients with COVID-19, and 20% of those hospitalized, experience severe symptoms necessitating intensive care. More than 75% of patients hospitalized with COVID-19 require supplemental oxygen. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care (21.6% vs 24.6%; age-adjusted rate ratio, 0.83 [95% CI, 0.74-0.92]) and that remdesivir improves time to recovery (hospital discharge or no supplemental oxygen requirement) from 15 to 11 days. In a randomized trial of 103 patients with COVID-19, convalescent plasma did not shorten time to recovery. Ongoing trials are testing antiviral therapies, immune modulators, and anticoagulants. The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%. At least 120 SARS-CoV-2 vaccines are under development. Until an effective vaccine is available, the primary methods to reduce spread are face masks, social distancing, and contact tracing. Monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies. Conclusions and Relevance As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions.

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09/07/2020 Articles
SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on viru...

SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects

NATURE

Authors
Antoni G. Wrobel, Donald J. Benton, Pengqi Xu, Chloë Roustan, Stephen R. Martin, Peter B. Rosenthal, John J. Skehel, Steven J. Gamblin



ABSTRACT
SARS-CoV-2 is thought to have emerged from bats, possibly via a secondary host. Here, we investigate the relationship of spike (S) glycoprotein from SARS-CoV-2 with the S protein of a closely related bat virus, RaTG13. We determined cryo-EM structures for RaTG13 S and for both furin-cleaved and uncleaved SARS-CoV-2 S; we compared these with recently reported structures for uncleaved SARS-CoV-2 S. We also biochemically characterized their relative stabilities and affinities for the SARS-CoV-2 receptor ACE2. Although the overall structures of human and bat virus S proteins are similar, there are key differences in their properties, including a more stable precleavage form of human S and about 1,000-fold tighter binding of SARS-CoV-2 to human receptor. These observations suggest that cleavage at the furin-cleavage site decreases the overall stability of SARS-CoV-2 S and facilitates the adoption of the open conformation that is required for S to bind to the ACE2 receptor.

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07/07/2020 Articles
SARS-CoV-2 in fruit bats, ferrets, pigs, and chickens: an experimental...

SARS-CoV-2 in fruit bats, ferrets, pigs, and chickens: an experimental transmission study

THE LANCET

Authors
Kore Schlottau, Melanie Rissmann, Annika Graaf, Jacob Schön, Julia Sehl, Claudia Wylezich, Dirk Höper, Thomas C Mettenleiter, Anne Balkema-Buschmann, Timm Harder, Christian Grund, Donata Hoffmann, Angele Breithaupt, Martin Beer


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07/07/2020 News
Covid-19: Airborne transmission is being underestimated, warn experts

THE BMJ

Authors
Owen Dyer


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07/07/2020 New Result
The Spike D614G mutation increases SARS-CoV-2 infection of multiple hu...

The Spike D614G mutation increases SARS-CoV-2 infection of multiple human cell types

BIORXIV

Authors
Zharko Daniloski, Tristan X. Jordan, Juliana K. Ilmain, Xinyi Guo, Gira Bhabha, Benjamin R. tenOever, Neville E. Sanjana

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06/07/2020 Articles
Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccin...

Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment

SCIENCE

Authors
Jing Sun, Zhen Zhuang, Jian Zheng, Paul B. McCray, Jr., Stanley Perlman, Jincun Zhao


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03/07/2020 Preview
Making sense of mutation: what D614G means for the COVID-19 pandemic r...

Making sense of mutation: what D614G means for the COVID-19 pandemic remains unclear

SCIENCE DIRECT

Authors
Nathan D. Grubaugh, William P. Hanage, Angela L. Rasmussen



ABSTRACT
Korber et al. (2020) found that a SARS-CoV-2 variant in the spike protein, D614G, rapidly became dominant around the world. While clinical and in vitro data suggest that D614G changes the virus phenotype, the impact of the mutation on transmission, disease, and vaccine and therapeutic development are largely unknown.

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02/07/2020 Reviews
Using heat to kill SARS‐CoV ‐2

WILEY ONLINE LIBRARY

Authors
John P. Abraham, Brian D. Plourde, Lijing Cheng


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01/07/2020 Articles
Coronaviruses and SARS-CoV-2: A Brief Overview

ANESTHESIA & ANALGESIA

Authors
Ludwig, Stephan, Zarbock, Alexander



ABSTRACT
In late December 2019, several cases of pneumonia of unknown origin were reported from China, which in early January 2020 were announced to be caused by a novel coronavirus. The virus was later denominated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and defined as the causal agent of coronavirus disease 2019 (COVID-19). Despite massive attempts to contain the disease in China, the virus has spread globally, and COVID-19 was declared a pandemic by the World Health Organization (WHO) in March 2020. Here we provide a short background on coronaviruses, and describe in more detail the novel SARS-CoV-2 and attempts to identify effective therapies against COVID-19.

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29/06/2020 Articles
Lower nasopharyngeal viral load during the latest phase of COVID-19 pa...

Lower nasopharyngeal viral load during the latest phase of COVID-19 pandemic in a Northern Italy University Hospital

DE GRUYTER

Authors
Nicola Clementi, Roberto Ferrarese, Marco Tonelli, Virginia Amato, Sara Racca, Massimo Locatelli, Giuseppe Lippi, Guido Silvestri, Massimo Clementi, Nicasio Mancini



ABSTRACT
Objectives A milder clinical course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been anecdotally reported over the latest phase of COVID-19 pandemic in Italy. Several factors may contribute to this observation, including the effect of lockdown, social distancing, lower humidity, lower air pollution, and potential changes in the intrinsic pathogenicity of the virus. In this regard, the clinical severity of COVID-19 could be attenuated by mutations in SARS-CoV-2 genome that decrease its virulence, as well as by lower virus inocula.
Methods In this pilot study, we compared the reverse transcription polymerase chain reaction (RT-PCR) amplification profile of 100 nasopharyngeal swabs consecutively collected in April, during the peak of SARS-CoV-2 epidemic, to that of 100 swabs collected using the same procedure in May.
Results The mean Ct value of positive samples collected in May was significantly higher than that of samples collected in the previous period (ORF 1a/b gene: 31.85 ± 0.32 vs. 28.37 ± 0.5, p<0.001; E gene: 33.76 ± 0.38 vs. 29.79 ± 0.63, p<0.001), suggesting a lower viral load at the time of sampling. No significant differences were observed between male and females in the two periods, whilst higher viral loads were found in (i) patients over 60-years old, and (ii) patients that experienced severe COVID-19 during the early stages of the pandemic.
Conclusions This pilot study prompts further investigation on the correlation between SARS-CoV-2 load and different clinical manifestation of COVID-19 during different phases of the pandemic. Laboratories should consider reporting quantitative viral load data in the molecular diagnosis of SARS-CoV-2 infection.

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23/06/2020 Reviews
The history and value of face masks

EUROPEAN MEDICAL OF RESEARCH

Authors
Christiane Matuschek, Friedrich Moll, Heiner Fangerau, Johannes C. Fischer, Kurt Zänker, Martijn van Griensven, Marion Schneider, Detlef Kindgen-Milles, Wolfram Trudo Knoefel, Artur Lichtenberg, Bálint Tamaskovics, Freddy Joel Djiepmo-Njanang, Wilfried Budach, Stefanie Corradini, Dieter Häussinger, Torsten Feldt, Björn Jensen, Rainer Pelka, Klaus Orth, Matthias Peiper, Olaf Grebe, Kitti Maas, Edwin Bölke, Jan Haussmann



ABSTRACT
In the human population, social contacts are a key for transmission of bacteria and viruses. The use of face masks seems to be critical to prevent the transmission of SARS-CoV-2 for the period, in which therapeutic interventions are lacking. In this review, we describe the history of masks from the middle age to modern times.

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22/06/2020 News
Mini organs reveal how the coronavirus ravages the body

NATURE

Authors
Smriti Mallapaty


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22/06/2020 News
Going back in time for an antibody to fight COVID-19

NATURE

Authors
Gary R. Whittaker, Susan Daniel


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18/06/2020 Articles
The receptor binding domain of the viral spike protein is an immunodom...

The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients

SCIENCE

Authors
Lakshmanane Premkumar, Bruno Segovia-Chumbez , Ramesh Jadi, David R. Martinez, Rajendra Raut, Alena Markmann, Caleb Cornaby, Luther Bartelt, Susan Weiss, Yara Park, Caitlin E. Edwards, Eric Weimer, Erin M. Scherer, Nadine Rouphael, Srilatha Edupuganti, Daniela Weiskopf, Longping V. Ts, Yixuan J. Hou, David Margolis, Alessandro Sette, Matthew H. Collins, John Schmitz, Ralph S. Baric, Aravinda M. de Silva



ABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that first emerged in late 2019 is responsible for a pandemic of severe respiratory illness. People infected with this highly contagious virus can present with clinically inapparent, mild, or severe disease. Currently, the virus infection in individuals and at the population level is being monitored by PCR testing of symptomatic patients for the presence of viral RNA. There is an urgent need for SARS-CoV-2 serologic tests to identify all infected individuals, irrespective of clinical symptoms, to conduct surveillance and implement strategies to contain spread. As the receptor binding domain (RBD) of the spike protein is poorly conserved between SARS-CoVs and other pathogenic human coronaviruses, the RBD represents a promising antigen for detecting CoV-specific antibodies in people. Here we use a large panel of human sera (63 SARS-CoV-2 patients and 71 control subjects) and hyperimmune sera from animals exposed to zoonotic CoVs to evaluate RBD's performance as an antigen for reliable detection of SARS-CoV-2-specific antibodies. By day 9 after the onset of symptoms, the recombinant SARS-CoV-2 RBD antigen was highly sensitive (98%) and specific (100%) for antibodies induced by SARS-CoVs. We observed a strong correlation between levels of RBD binding antibodies and SARS-CoV-2 neutralizing antibodies in patients. Our results, which reveal the early kinetics of SARS-CoV-2 antibody responses, support using the RBD antigen in serological diagnostic assays and RBD-specific antibody levels as a correlate of SARS-CoV-2 neutralizing antibodies in people.

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18/06/2020 Letter
Severe Acute Respiratory Syndrome Coronavirus 2-Specific Antibodies in...

Severe Acute Respiratory Syndrome Coronavirus 2-Specific Antibodies in Pets in Wuhan, China

Authors
Jianjun Chen , Chaolin Huang , Yanan Zhang , Sai Zhang , Meilin Jin


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17/06/2020 Articles
Evidence for host-dependent RNA editing in the transcriptome of SARS-C...

Evidence for host-dependent RNA editing in the transcriptome of SARS-CoV-2

SCIENCE

Authors
Salvatore DiGiorgio, Filippo Martignano, Maria Gabriella Torcia, Giorgio Mattiuz, Silvestro G. Conticello



ABSTRACT
The COVID-19 outbreak has become a global health risk, and understanding the response of the host to the SARS-CoV-2 virus will help to combat the disease. RNA editing by host deaminases is an innate restriction process to counter virus infection, but it is not yet known whether this process operates against coronaviruses. Here, we analyze RNA sequences from bronchoalveolar lavage fluids obtained from coronavirus-infected patients. We identify nucleotide changes that may be signatures of RNA editing: adenosine-to-inosine changes from ADAR deaminases and cytosine-to-uracil changes from APOBEC deaminases. Mutational analysis of genomes from different strains of Coronaviridae from human hosts reveals mutational patterns consistent with those observed in the transcriptomic data. However, the reduced ADAR signature in these data raises the possibility that ADARs might be more effective than APOBECs in restricting viral propagation. Our results thus suggest that both APOBECs and ADARs are involved in coronavirus genome editing, a process that may shape the fate of both virus and patient.

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17/06/2020 Articles
Genomewide Association Study of Severe Covid-19 with Respiratory Failu...

Genomewide Association Study of Severe Covid-19 with Respiratory Failure

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
The Severe Covid-19 GWAS Group



ABSTRACT
BACKGROUND
There is considerable variation in disease behavior among patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19). Genomewide association analysis may allow for the identification of potential genetic factors involved in the development of Covid-19.
METHODS We conducted a genomewide association study involving 1980 patients with Covid-19 and severe disease (defined as respiratory failure) at seven hospitals in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe. After quality con- trol and the exclusion of population outliers, 835 patients and 1255 control par- ticipants from Italy and 775 patients and 950 control participants from Spain were included in the final analysis. In total, we analyzed 8,582,968 single-nucleotide polymorphisms and conducted a meta-analysis of the two case–control panels.
RESULTS We detected cross-replicating associations with rs11385942 at locus 3p21.31 and with rs657152 at locus 9q34.2, which were significant at the genomewide level (P<5×10−8) in the meta-analysis of the two case–control panels (odds ratio, 1.77; 95% confidence interval [CI], 1.48 to 2.11; P=1.15×10−10; and odds ratio, 1.32; 95% CI, 1.20 to 1.47; P=4.95×10−8, respectively). At locus 3p21.31, the association signal spanned the genes SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1. The association signal at locus 9q34.2 coincided with the ABO blood group locus; in this cohort, a blood-group–specific analysis showed a higher risk in blood group A than in other blood groups (odds ratio, 1.45; 95% CI, 1.20 to 1.75; P=1.48×10−4) and a protective effect in blood group O as compared with other blood groups (odds ratio, 0.65; 95% CI, 0.53 to 0.79; P=1.06×10−5).
CONCLUSIONS We identified a 3p21.31 gene cluster as a genetic susceptibility locus in patients with Covid-19 with respiratory failure and confirmed a potential involvement of the ABO blood-group system. (Funded by Stein Erik Hagen and others.)


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17/06/2020 Reviews
Vaccines against Coronaviruses: The State of the Art

MDPI

Authors
Cristiano Conte, Francesco Sogni , Paola Affanni , Licia Veronesi , Alberto Argentiero, Susanna Esposito



ABSTRACT
The emerging epidemic caused by the new coronavirus SARS-CoV-2 represents the most important socio-health threat of the 21st century. The high contagiousness of the virus, the strong impact on the health system of the various countries and the absence to date of treatments able to improve the prognosis of the disease make the introduction of a vaccine indispensable, even though there are currently no approved human coronavirus vaccines. The aim of the study is to carry out a review of the medical literature concerning vaccine candidates for the main coronaviruses responsible for human epidemics, including recent advances in the development of a vaccine against COVID-19. This extensive review carried out on the vaccine candidates of the main epidemic coronaviruses of the past has shown that the studies in animal models suggest a high efficacy of potential vaccines in providing protection against viral challenges. Similar human studies have not yet been carried out, as the main trials are aimed at assessing mainly vaccine safety and immunogenicity. Whereas the severe acute respiratory syndrome (SARS-CoV) epidemic ended almost two decades ago and the Middle East respiratory syndrome (MERS-CoV) epidemic is now better controlled, as it is less contagious due to the high lethality of the virus, the current SARS-CoV-2 pandemic represents a problem that is certainly more compelling, which pushes us to accelerate the studies not only for the production of vaccines but also for innovative pharmacological treatments. SARS-CoV-2 vaccines might come too late to affect the first wave of this pandemic, but they might be useful if additional subsequent waves occur or in a post-pandemic perspective in which the virus continues to circulate as a seasonal virus.

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16/06/2020 Primer
Respiratory Virus Infections: Understanding COVID-19

SCIENCE DIRECT

Authors
Kanta Subbarao, Siddhartha Mahanty



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04/06/2020 Viewpoint
Responding to the COVID-19 Pandemic The Need for a Structurally Compet...

Responding to the COVID-19 Pandemic The Need for a Structurally Competent Health Care System

JAMA

Authors
Jonathan M. Metzl, Aletha Maybank; Fernando De Maio

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03/06/2020 Short Communication
Evidence for mutations in SARS-CoV-2 Italian isolates potentially affe...

Evidence for mutations in SARS-CoV-2 Italian isolates potentially affecting virus transmission

JOURNAL OF MEDICAL VIROLOGY

Authors
Domenico Benvenuto Ayse Banu Demir Marta Giovanetti Martina Bianchi Silvia Angeletti Stefano Pascarella Roberto Cauda Massimo Ciccozzi Antonio Cassone

ABSTRACT Italy is the first western country suffering heavy SARS‐CoV‐2 transmission and disease impact after Covid‐19 pandemia started in China. Even though the presence of mutations on spike glycoprotein and nucleocapsid in Italian isolates has been reported, the potential impact of these mutations on viral transmission has not been evaluated. We have compared SARS‐CoV‐2 genome sequences from Italian patients with virus sequences from Chinese patients. We focussed upon three non‐synonimous mutations of genes coding for S(one) and N (two) viral proteins present in Italian isolates and absent in Chinese ones, using various bio‐informatic tools. Amino acid analysis and changes in three‐dimensional protein structure suggests the mutations reduce protein stability and, particularly for S1 mutation, the enhanced torsional ability of the molecule could favour virus binding to cell receptor(s). This theoretical interpretation awaits experimental and clinical confirmation.

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27/05/2020 Comment
Small droplet aerosols in poorly ventilated spaces and SARS-CoV-2 tran...

Small droplet aerosols in poorly ventilated spaces and SARS-CoV-2 transmission

The Lancet

Authors
G Aernout Somsen, Cees van Rijn, Stefan Kooij, Reinout A Bem, Daniel Bonn

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20/05/2020 Article
How to Discover Antiviral Drugs Quickly

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Jerry M. Parks, Jeremy C. Smith

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19/05/2020 Advanced Research
COVID-19 infection: Origin, transmission, and characteristics of human...

COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses

Science Direct

Authors
Muhammad AdnanShereen, Suliman Khana, AbeerKazmic, NadiaBashira, Rabeea Siddique

ABSTRACT

The coronavirus disease 19 (COVID-19) is a highly transmittable and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in Wuhan, China and spread around the world. Genomic analysis revealed that SARS-CoV-2 is phylogenetically related to severe acute respiratory syndrome-like (SARS-like) bat viruses, therefore bats could be the possible primary reservoir. The intermediate source of origin and transfer to humans is not known, however, the rapid human to human transfer has been confirmed widely. There is no clinically approved antiviral drug or vaccine available to be used against COVID-19. However, few broad-spectrum antiviral drugs have been evaluated against COVID-19 in clinical trials, resulted in clinical recovery. In the current review, we summarize and comparatively analyze the emergence and pathogenicity of COVID-19 infection and previous human coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV). We also discuss the approaches for developing effective vaccines and therapeutic combinations to cope with this viral outbreak.

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18/05/2020 Research Article
Evidence for host-dependent RNA editing in the transcriptome of SARS-C...

Evidence for host-dependent RNA editing in the transcriptome of SARS-CoV-2 in humans

SCIENCE

Authors
Salvatore Di Giorgio, Filippo Martignano, Maria Gabriella Torcia, Giorgio Mattiuz, Silvestro G. Conticello

ABSTRACT

The COVID-19 outbreak has become a global health risk and understanding the response of the host to the SARS-CoV-2 virus will help to contrast the disease. Editing by host deaminases is an innate restriction process to counter viruses, and it is not yet known whether it operates against Coronaviruses. Here we analyze RNA sequences from bronchoalveolar lavage fluids derived from infected patients. We identify nucleotide changes that may be signatures of RNA editing: Adenosine-to-Inosine changes from ADAR deaminases and Cytosine-to-Uracil changes from APOBEC ones. A mutational analysis of genomes from different strains of human-hosted Coronaviridae reveals mutational patterns compatible to those observed in the transcriptomic data. Our results thus suggest that both APOBECs and ADARs are involved in Coronavirus genome editing, a process that may shape the fate of both virus and patient.

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18/05/2020 Arts and Culture
How to Draw the Coronavirus

THE PARIS REVIEW

Authors
Rebekah Frumkin

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14/05/2020 Opinion
No evidence for distinct types in the evolution of SARS-CoV-2

OXFORD ACADEMY

Authors
Oscar A. MacLean, Richard J. Orton, Joshua B. Singer, David L. Robertson

ABSTRACT

A recent study by Tang et al. claimed that two major types of severe acute respiratory syndrome-coronavirus-2 (CoV-2) had evolved in the ongoing CoV disease-2019 pandemic and that one of these types was more ‘aggressive’ than the other. Given the repercussions of these claims and the intense media coverage of these types of articles, we have examined in detail the data presented by Tang et al., and show that the major conclusions of that paper cannot be substantiated. Using examples from other viral outbreaks, we discuss the difficulty in demonstrating the existence or nature of a functional effect of a viral mutation, and we advise against overinterpretation of genomic data during the pandemic.

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11/05/2020 Report
A Novel Bat Coronavirus Closely Related to SARS-CoV-2 Contains Natural...

A Novel Bat Coronavirus Closely Related to SARS-CoV-2 Contains Natural Insertions...

SCIENCE DIRECT

Authors
Hong Zhou, Xing Chen, Tao Hu, Juan Li, Hao Song, Yanran Liu, Peihan Wang, Di Liu, Jing Yang, Edward C. Holmes, Alice C. Hughes, Yuhai Bi, Weifeng Shi

ABSTRACT The unprecedented pandemic of pneumonia caused by a novel coronavirus, SARS-CoV-2, in China and beyond has had major public health impacts on a global scale [1, 2]. Although bats are regarded as the most likely natural hosts for SARS-CoV-2 [3], the origins of the virus remain unclear. Here, we report a novel bat-derived coronavirus, denoted RmYN02, identified from a metagenomic analysis of samples from 227 bats collected from Yunnan Province in China between May and October 2019. Notably, RmYN02 shares 93.3% nucleotide identity with SARS-CoV-2 at the scale of the complete virus genome and 97.2% identity in the 1ab gene, in which it is the closest relative of SARS-CoV-2 reported to date. In contrast, RmYN02 showed low sequence identity (61.3%) to SARS-CoV-2 in the receptor-binding domain (RBD) and might not bind to angiotensin-converting enzyme 2 (ACE2). Critically, and in a similar manner to SARS-CoV-2, RmYN02 was characterized by the insertion of multiple amino acids at the junction site of the S1 and S2 subunits of the spike (S) protein. This provides strong evidence that such insertion events can occur naturally in animal betacoronaviruses.

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08/05/2020 Report
A highly conserved cryptic epitope in the receptor binding domains of ...

A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2...

SCIENCE

Authors
Meng Yuan, Nicholas C. Wu, Xueyong Zhu, Chang-Chun D. Lee, Ray T. Y. So, Huibin Lv, Chris K. P. Mok, Ian A. Wilson

ABSTRACT

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) has now become a pandemic, but there is currently very little understanding of the antigenicity of the virus. We therefore determined the crystal structure of CR3022, a neutralizing antibody previously isolated from a convalescent SARS patient, in complex with the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein at 3.1-angstrom resolution. CR3022 targets a highly conserved epitope, distal from the receptor binding site, that enables cross-reactive binding between SARS-CoV-2 and SARS-CoV. Structural modeling further demonstrates that the binding epitope can only be accessed by CR3022 when at least two RBDs on the trimeric S protein are in the “up” conformation and slightly rotated. These results provide molecular insights into antibody recognition of SARS-CoV-2.

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07/05/2020 Link
Genomic epidemiology of novel coronavirus - Global subsampling

NEXSTRAIN

Authors
NEXSTRAIN

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04/05/2020 News
Profile of a killer the complex biology powering the coronavirus pande...

Profile of a killer the complex biology powering the coronavirus pandemic

Nature

Authors
David Cyranoski

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04/05/2020 Report
Inquinamento atmosferico e diffusione del virus SARS-CoV-2

ISTITUTO SUPERIORE DI SANITA'

Authors
ISTITUTO SUPERIORE DI SANITA'


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01/05/2020 Articles
SARS-CoV-2 productively infects human gut enterocytes

Science

Authors
Mart M. Lamers, Joep Beumer, Jelte van der Vaart,, Kèvin Knoops, Jens Puschhof, Tim I. Breugem1, Raimond B. G. Ravelli, J. Paul van Schayck, Anna Z. Mykytyn, Hans Q. Duimel, Elly van Donselaar, Samra Riesebosch, Helma J. H. Kuijpers, Debby Schippers, Willine J. van de Wetering, Miranda de Graaf, Marion Koopmans, Edwin Cuppen, Peter J. Peters, Bart L. Haagmans, Hans Clevers

ABSTRACT


The virus severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) can cause coronavirus disease 2019 (COVID-19), an influenza-like disease that is primarily thought to infect the lungs with transmission via the respiratory route. However, clinical evidence suggests that the intestine may present another viral target organ. Indeed, the SARS-CoV-2 receptor angiotensin converting enzyme 2 (ACE2) is highly expressed on differentiated enterocytes. In human small intestinal organoids (hSIOs), enterocytes were readily infected by SARS-CoV and SARS-CoV-2 as demonstrated by confocal- and electron-microscopy. Consequently, significant titers of infectious viral particles were detected. mRNA expression analysis revealed strong induction of a generic viral response program. Hence, intestinal epithelium supports SARS-CoV-2 replication, and hSIOs serve as an experimental model for coronavirus infection and biology


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29/04/2020 New Result
Spike mutation pipeline reveals the emergence of a more transmissible ...

Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2

bioRxiv

Authors
Werner Abfalterer, Brian Foley, Elena E Giorgi, Tanmoy Bhattacharya, Matthew D Parker, David G Partridge, Cariad M Evans,Thushan de Silva, Celia C LaBranche, David C Montefiori

Abstract

We have developed an analysis pipeline to facilitate real-time mutation tracking in SARS-CoV-2, focusing initially on the Spike (S) protein because it mediates infection of human cells and is the target of most vaccine strategies and antibody-based therapeutics. To date we have identified fourteen mutations in Spike that are accumulating. Mutations are considered in a broader phylogenetic context, geographically, and over time, to provide an early warning system to reveal mutations that may confer selective advantages in transmission or resistance to interventions. Each one is evaluated for evidence of positive selection, and the implications of the mutation are explored through structural modeling. The mutation Spike D614G is of urgent concern; after beginning to spread in Europe in early February, when introduced to new regions it repeatedly and rapidly becomes the dominant form. Also, we present evidence of recombination between locally circulating strains, indicative of multiple strain infections. These finding have important implications for SARS-CoV-2 transmission, pathogenesis and immune interventions.

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21/04/2020 Articles
Comparative tropism, replication kinetics, and cell damage profiling o...

Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV...

The Lancet

Authors
Hin Chu, Jasper Fuk-Woo Chan, Terrence Tsz-Tai Yuen, Huiping Shuai, Shuofeng Yuan, Yixin Wang, Bingjie Hu, Cyril Chik-Yan Yip, Jessica Oi-Ling Tsang, Xiner Huang, Yue Chai, Dong Yang, Yuxin Hou, Kenn Ka-Heng Chik, Xi Zhang, Agnes Yim-Fong Fung, Hoi-Wah Tsoi, Jian-Piao Cai, Wan-Mui Chan, Jonathan Daniel Ip, Allen Wing-Ho Chu, Jie Zhou, David Christopher Lung, Kin-Hang Kok, Kelvin Kai-Wang To, Owen Tak-Yin Tsang, Kwok-Hung Chan, Kwok-Yung Yuen

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21/04/2020 Comment
SARS-CoV-2 cellular tropism

The Lancet

Authors
VALERIA CAGNO

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19/04/2020 Abstract
Recent progress and challenges in drug development against COVID-19...

NCBI

Authors
Tarek Mohamed Abd El-Aziza, James D. Stockanda

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18/04/2020 World Report
Flooded by the torrent: the COVID-19 drug pipeline

The Lancet

Authors
Asher Mullard

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17/04/2020 Letter
SARS-CoV-2 Isolation From Ocular Secretions of a Patient With COVID-19...

SARS-CoV-2 Isolation From Ocular Secretions of a Patient With COVID-19 in Italy...

ANNALS OF INTERNAL MEDICINE

Authors
Francesca Colavita, Daniele Lapa, Fabrizio Carletti, Eleonora Lalle, Licia Bordi, Patrizia Marsella, Emanuele Nicastri, Nazario Bevilacqua, Maria Letizia Giancola, Angela Corpolongo, Giuseppe Ippolito, Maria Rosaria Capobianchi, Concetta Castilletti,

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16/04/2020 Correspondence
Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-...

Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Neeltje van Doremalen, Trenton Bushmaker, Dylan H. Morris, Myndi G. Holbrook, Amandine Gamble, Brandi N. Williamson, Azaibi Tamin, Jennifer L. Harcourt, Natalie J. Thornburg, Susan I. Gerber, James O. Lloyd-Smith, Emmie de Wit, Vincent J. Munster

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16/04/2020 Articles
SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a ...

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

SCIENCE DIRECT

Authors
Markus Hoffmann, Hannah Kleine-Weber, Simon Schroeder, Nadine Kruger, Tanja Herrler, Sandra Erichsen, Tobias S. Schiergens, Georg Herrler, Nai-Huei Wu, Andreas Nitsche, Marcel A. Muller, Christian Drosten and Stefan Pohlmann

Summary 

The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.

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16/04/2020 News
Covid-19: First coronavirus was described in The BMJ in 1965

THE BMJ

Authors
Elisabeth Mahase

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15/04/2020 Correspondence
Droplets and Aerosols in the Transmission of SARS-CoV-2

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Matthew Meselson

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15/04/2020 Communication
Temporal dynamics in viral shedding and transmissibility of COVID-19

NATURE MEDICINE

Authors
Xi He, Eric H. Y. Lau, Peng Wu, Xilong Deng, Jian Wang, Xinxin Hao, Yiu Chung Lau ,Jessica Y. Wong, Yujuan Guan, Xinghua Tan, Xiaoneng Mo, Yanqing Chen, Baolin Liao, Weilie Chen, Fengyu Hu, Qing Zhang, Mingqiu Zhong, Yanrong Wu, Lingzhai Zhao, Fuchun Zhang, Benjamin J. Cowling, Fang Li and Gabriel M. Leung

ABSTRACT

We report temporal patterns of viral shedding in 94 patients with laboratory-confirmed COVID-19 and modeled COVID-19 infectiousness profiles from a separate sample of 77 infector–infectee transmission pairs. We observed the highest viral load in throat swabs at the time of symptom onset, and inferred that infectiousness peaked on or before symptom onset. We estimated that 44% (95% confidence interval, 25–69%) of secondary cases were infected during the index cases’ presymptomatic stage, in settings with substantial household clustering, active case finding and quarantine outside the home. Disease control measures should be adjusted to account for probable substantial presymptomatic transmission.

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10/04/2020 Report
Structure of the RNA-dependent RNA polymerase from COVID-19 virus

SCIENCE

Authors
Yan Gao, Liming Yan,Yucen Huang, Fengjiang Liu, Yao Zhao, Lin Cao, Tao Wang, Qianqian Sun,Zhenhua Ming, Lianqi Zhang, Ji Ge, Litao Zheng, Ying Zhan, Haofeng Wang, Yan Zhu,Chen Zhu,Tianyu Hu, Tian Hua, Bing Zhang, Xiuna Yang, Jun Li, Haitao Yang, Zhijie Liu, Wenqing Xu, Luke W.Guddat, Quan Wang, Zhiyong Lou, Zihe Rao

ABSTRACT 

A novel coronavirus (COVID-19 virus) outbreak has caused a global pandemic resulting in tens of thousands of infections and thousands of deaths worldwide. The RNA-dependent RNA polymerase (RdRp, also named nsp12) is the central component of coronaviral replication/transcription machinery and appears to be a primary target for the antiviral drug, remdesivir. We report the cryo-EM structure of COVID-19 virus full-length nsp12 in complex with cofactors nsp7 and nsp8 at 2.9-Å resolution. In addition to the conserved architecture of the polymerase core of the viral polymerase family, nsp12 possesses a newly identified β-hairpin domain at its N terminus. A comparative analysis model shows how remdesivir binds to this polymerase. The structure provides a basis for the design of new antiviral therapeutics targeting viral RdRp.

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09/04/2020 Articles
Structure of Mpro from COVID-19 virus and discovery of its inhibitors

CSH LABORATORY

Authors
Zhenming Jin, Xiaoyu Du, Yechun Xu, Yongqiang Deng, Meiqin Liu, Yao Zhao, Bing Zhang, Xiaofeng Li, Leike Zhang, Chao Peng, Yinkai Duan, Jing Yu, Lin Wang, Kailin Yang, Fengjiang Liu, Rendi Jiang, Xinglou Yang, Tian You, Xiaoce Liu, Xiuna Yang, Fang Bai, Hong Liu, Xiang Liu, Luke W. Guddat, Wenqing Xu, Gengfu Xiao, Chengfeng Qin, Zhengli Shi, Hualiang Jiang, Zihe Rao &amp; Haitao Yang

Abstract

A new coronavirus (CoV) identified as COVID-19 virus is the etiological agent responsible for the 2019-2020 viral pneumonia outbreak that commenced in Wuhan1-4. Currently there is no targeted therapeutics and effective treatment options remain very limited. In order to rapidly discover lead compounds for clinical use, we initiated a program of combined structure-assisted drug design, virtual drug screening and high-throughput screening to identify new drug leads that target the COVID-19 virus main protease (Mpro). Mpro is a key CoV enzyme, which plays a pivotal role in mediating viral replication and transcription, making it an attractive drug target for this virus5,6. Here, we identified a mechanism-based inhibitor, N3, by computer-aided drug design and subsequently determined the crystal structure of COVID-19 virus Mpro in complex with this compound. Next, through a combination of structure-based virtual and high-throughput screening, we assayed over 10,000 compounds including approved drugs, drug candidates in clinical trials, and other pharmacologically active compounds as inhibitors of Mpro. Six of these inhibit Mpro with IC50 values ranging from 0.67 to 21.4 μM. Ebselen also exhibited strong antiviral activity in cell-based assays. Our results demonstrate the efficacy of this screening strategy, which can lead to the rapid discovery of drug leads with clinical potential in response to new infectious diseases where no specific drugs or vaccines are available.

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08/04/2020 New Result
Genomic determinants of pathogenicity in SARS-CoV-2 and other human co...

Genomic determinants of pathogenicity in SARS-CoV-2 and other human coronaviruses

BIORXIV

Authors
Ayal B. Gussow, Noam Auslander, Yuri I. Wolf, Eugene V. Koonin



ABSTRACT
SARS-CoV-2 poses an immediate, urgent and major threat to public health across the globe. Here we report an in-depth molecular analysis to reconstruct the evolutionary origins of the enhanced pathogenicity of SARS-CoV-2 and other coronaviruses that are severe human pathogens. Using integrated comparative genomics and machine learning techniques, we identify key genomic features that differentiate SARS-CoV-2 and the viruses behind the two previous coronavirus outbreaks, SARS-CoV and MERS-CoV, from less pathogenic coronaviruses. The identified features could be crucial elements of coronavirus pathogenicity and possible targets for diagnostics, prognostication and interventions.

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08/04/2020 Articles
Phylogenetic network analysis of SARS-CoV-2 genomes

PNAS

Authors
Peter Forstera, Lucy Forsterd, Colin Renfrewb, Michael Forsterc

Summary

 In a phylogenetic network analysis of 160 complete human severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) genomes, we find three central variants distinguished by amino acid changes, which we have named A, B, and C, with A being the ancestral type according to the bat outgroup coronavirus. The A and C types are found in significant proportions outside East Asia, that is, in Europeans and Americans. In contrast, the B type is the most common type in East Asia, and its ancestral genome appears not to have spread outside East Asia without first mutating into derived B types, pointing to founder effects or immunological or environmental resistance against this type outside Asia. The network faithfully traces routes of infections for documented coronavirus disease 2019 (COVID-19) cases, indicating that phylogenetic networks can likewise be successfully used to help trace undocumented COVID-19 infection sources, which can then be quarantined to prevent recurrent spread of the disease worldwide. 

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02/04/2020 Communication
Whole genome and phylogenetic analysis of two SARS-CoV-2 strains isola...

Whole genome and phylogenetic analysis of two SARS-CoV-2 strains isolated in Italy...

Eurosurveillance

Authors
Paola Stefanelli , Giovanni Faggioni , Alessandra Lo Presti , Stefano Fiore , Antonella MarchI , Eleonora BenedettI , Concetta FabianI , Anna Anselmo, Andrea Ciammaruconi , Antonella Fortunato , Riccardo De Santis, Silvia Fillo, MariaRosaria Capobianchi , Maria Rita Gismondo , Alessandra Ciervo , Giovanni Rezza , Maria Rita Castrucci , Florigio Lista , on behalf of ISS COVID-19 study group6

Abstract
Whole genome sequences of SARS-CoV-2 obtained from two patients, a Chinese tourist visiting Rome and an Italian, were compared with sequences from Europe and elsewhere. In a phylogenetic tree, the Italian patient’s sequence clustered with sequences from Germany while the tourist’s sequence clustered with other European sequences. Some additional European sequences in the tree segregated outside the two clusters containing the patients’ sequences. This suggests multiple SARS-CoV-2 introductions in Europe or virus evolution during circulation.

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30/03/2020 Articles
Estimates of the severity of coronavirus disease 2019: a model-based a...

Estimates of the severity of coronavirus disease 2019: a model-based analysis

The Lancet

Authors
Robert Verity, Lucy C Okell, Ilaria Dorigatti*, Peter Winskill, Charles Whittaker, Natsuko Imai, Gina Cuomo-Dannenburg, Hayley Thompson, Patrick G T Walker, Han Fu, Amy Dighe, Jamie T Griffin, Marc Baguelin, Sangeeta Bhatia, Adhiratha Boonyasiri, Anne Cori, Zulma Cucunub&aacute;, Rich FitzJohn, Katy Gaythorpe, Will Green, Arran Hamlet, Wes Hinsley, Daniel Laydon, Gemma Nedjati-Gilani, Steven Riley, Sabine van Elsland, Erik Volz, Haowei Wang, Yuanrong Wang, Xiaoyue Xi, Christl A Donnelly, Azra C Ghani, Neil M Ferguson

ABSTRACT

Background

In the face of rapidly changing data, a range of case fatality ratio estimates for coronavirus disease 2019 (COVID-19) have been produced that differ substantially in magnitude. We aimed to provide robust estimates, accounting for censoring and ascertainment biases.

Findings

Using data on 24 deaths that occurred in mainland China and 165 recoveries outside of China, we estimated the mean duration from onset of symptoms to death to be 17·8 days (95% credible interval [CrI] 16·9–19·2) and to hospital discharge to be 24·7 days (22·9–28·1). In all laboratory confirmed and clinically diagnosed cases from mainland China (n=70117), we estimated a crude case fatality ratio (adjusted for censoring) of 3·67% (95% CrI 3·56–3·80). However, after further adjusting for demography and under-ascertainment, we obtained a best estimate of the case fatality ratio in China of 1·38% (1·23–1·53), with substantially higher ratios in older age groups (0·32% [0·27–0·38] in those aged <60 years vs 6·4% [5·7–7·2] in those aged ≥60 years), up to 13·4% (11·2–15·9) in those aged 80 years or older. Estimates of case fatality ratio from international cases stratified by age were consistent with those from China (parametric estimate 1·4% [0·4–3·5] in those aged <60 years [n=360] and 4·5% [1·8–11·1] in those aged ≥60 years [n=151]). Our estimated overall infection fatality ratio for China was 0·66% (0·39–1·33), with an increasing profile with age. Similarly, estimates of the proportion of infected individuals likely to be hospitalised increased with age up to a maximum of 18·4% (11·0–7·6) in those aged 80 years or older.We collected individual-case data for patients who died from COVID-19 in Hubei, mainland China (reported by national and provincial health commissions to Feb 8, 2020), and for cases outside of mainland China (from government or ministry of health websites and media reports for 37 countries, as well as Hong Kong and Macau, until Feb 25, 2020). These individual-case data were used to estimate the time between onset of symptoms and outcome (death or discharge from hospital). We next obtained age-stratified estimates of the case fatality ratio by relating the aggregate distribution of cases to the observed cumulative deaths in China, assuming a constant attack rate by age and adjusting for demography and age-based and location-based under-ascertainment. We also estimated the case fatality ratio from individual line-list data on 1334 cases identified outside of mainland China. Using data on the prevalence of PCR-confirmed cases in international residents repatriated from China, we obtained age-stratified estimates of the infection fatality ratio. Furthermore, data on age-stratified severity in a subset of 3665 cases from China were used to estimate the proportion of infected individuals who are likely to require hospitalisation.

Interpretation

These early estimates give an indication of the fatality ratio across the spectrum of COVID-19 disease and show a strong age gradient in risk of death.

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30/03/2020 Comment
Likelihood of survival of coronavirus disease 2019

The Lancet

Authors
Shigui Ruan

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30/03/2020 Articles
Estimating the number of infections and the impact of non-pharmaceutic...

Estimating the number of infections and the impact of non-pharmaceutical interventions....

Imperial College London

Authors
Seth Flaxman, , Swapnil Mishra, Axel Gandy, H Juliette T Unwin, Helen Coupland, Thomas A Mellan, Harrison Zhu, Tresnia Berah, Jeffrey W Eaton, Pablo N P Guzman, Nora Schmit, Lucia Cilloni, Kylie E C Ainslie, Marc Baguelin, Isobel Blake, Adhiratha Boonyasiri, Olivia Boyd, Lorenzo Cattarino, Constanze Ciavarella, Laura Cooper, Zulma Cucunub&aacute;, Gina Cuomo-Dannenburg, Amy Dighe, Bimandra Djaafara, Ilaria Dorigatti, Sabine van Elsland, Rich FitzJohn, Han Fu, Katy Gaythorpe, Lily Geidelberg, Nicholas Grassly, Will Green, Timothy Hallett, Arran Hamlet, Wes Hinsley, Ben Jeffrey, David Jorgensen, Edward Knock, Daniel Laydon, Gemma Nedjati-Gilani, Pierre Nouvellet, Kris Parag, Igor Siveroni, Hayley Thompson, Robert Verity, Erik Volz, Caroline Walters, Haowei Wang, Yuanrong Wang, Oliver Watson, Peter Winskill, Xiaoyue Xi, Charles Whittaker, Patrick GT Walker, Azra Ghani, Christl A. Donnelly, Steven Riley, Lucy C Okell, Michaela A C Vollmer, Neil M. Ferguson1 and Samir Bhatt

ABSTRACT

Following the emergence of a novel coronavirus (SARS-CoV-2) and its spread outside of China, Europe is now experiencing large epidemics. In response, many European countries have implemented unprecedented non-pharmaceutical interventions including case isolation, the closure of schools and universities, banning of mass gatherings and/or public events, and most recently, widescale social distancing including local and national lockdowns. In this report, we use a semi-mechanistic Bayesian hierarchical model to attempt to infer the impact of these interventions across 11 European countries. Our methods assume that changes in the reproductive number – a measure of transmission - are an immediate response to these interventions being implemented rather than broader gradual changes in behaviour. Our model estimates these changes by calculating backwards from the deaths observed over time to estimate transmission that occurred several weeks prior, allowing for the time lag between infection and death. One of the key assumptions of the model is that each intervention has the same effect on the reproduction number across countries and over time. This allows us to leverage a greater amount of data across Europe to estimate these effects. It also means that our results are driven strongly by the data from countries with more advanced epidemics, and earlier interventions, such as Italy and Spain. We find that the slowing growth in daily reported deaths in Italy is consistent with a significant impact of interventions implemented several weeks earlier. In Italy, we estimate that the effective reproduction number, Rt, dropped to close to 1 around the time of lockdown (11th March), although with a high level of uncertainty. Overall, we estimate that countries have managed to reduce their reproduction number. Our estimates have wide credible intervals and contain 1 for countries that have implemented all interventions considered in our analysis. This means that the reproduction number may be above or below this value. With current interventions remaining in place to at least the end of March, we estimate that interventions across all 11 countries will have averted 59,000 deaths up to 31 March [95% credible interval 21,000-120,000]. Many more deaths will be averted through ensuring that interventions remain in place until transmission drops to low levels. We estimate that, across all 11 countries between 7 and 43 million individuals have been infected with SARS-CoV-2 up to 28th March, representing between 1.88% and 11.43% of the population. The proportion of the population infected to date – the attack rate - is estimated to be highest in Spain followed by Italy and lowest in Germany and Norway, reflecting the relative stages of the epidemics. Given the lag of 2-3 weeks between when transmission changes occur and when their impact can be observed in trends in mortality, for most of the countries considered here it remains too early to be certain that recent interventions have been effective. If interventions in countries at earlier stages of their epidemic, such as Germany or the UK, are more or less effective than they were in the countries with advanced epidemics, on which our estimates are largely based, or if interventions have improved or worsened over time, then our estimates of the reproduction number and deaths averted would change accordingly. It is therefore critical that the current interventions remain in place and trends in cases and deaths are closely monitored in the coming days and weeks to provide reassurance that transmission of SARS-Cov-2 is slowing

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28/03/2020 Editorial
Covid-19 — Navigating the Uncharted

The New Egland Journal of Medicine

Authors
Anthony S. Fauci, Clifford Lane, Robert R. Redfield

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25/03/2020 Correspondence
Coordination of RECOVERY, RECOVERY-RS and PRINCIPLE trials

REMAP-CAP

Authors
REMAP-CAP

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25/03/2020 Overview
2019 Novel coronavirus (COVID-19) overview

SPRINGER LINK

Authors
Mehrdad Mohammadi, Maryam Meskini, Anderia Lucia do Nascimento Pinto

Abstract
Novel coronaviruses (CoVs) are zoonotic pathogens, but the first human-to-human transmission has been reported. CoVs have the best known genome of all RNA viruses, and mutations in the genome have now been found. A pneumonia of unknown cause detected in Wuhan, China, was first reported to the WHO Country Office in China on 31 December 2019. This study aims to report early findings related to COVID-19 and provide methods to prevent and treat it.

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23/03/2020 Viewpoint
Case-Fatality Rate and Characteristics of Patients Dying in Relation t...

Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy

JAMA

Authors
Graziano Onder, Giovanni Rezza, Silvio Brusaferro

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19/03/2020 Articles
Characterization of the receptor-binding domain (RBD) of 2019 novel co...

Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for...

Springer Nature

Authors
Wanbo Tai, Lei He, Xiujuan Zhang, Jing Pu, Denis Voronin, Shibo Jiang, Yusen Zhou, Lanying Du

The outbreak of Coronavirus Disease 2019 (COVID-19) has posed a serious threat to global public health, calling for the development of safe and effective prophylactics and therapeutics against infection of its causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as 2019 novel coronavirus (2019-nCoV). The CoV spike (S) protein plays the most important roles in viral attachment, fusion and entry, and serves as a target for development of antibodies, entry inhibitors and vaccines. Here, we identified the receptor-binding domain (RBD) in SARS-CoV-2 S protein and found that the RBD protein bound strongly to human and bat angiotensin-converting enzyme 2 (ACE2) receptors. SARS-CoV-2 RBD exhibited significantly higher binding affinity to ACE2 receptor than SARS-CoV RBD and could block the binding and, hence, attachment of SARS-CoV-2 RBD and SARS-CoV RBD to ACE2-expressing cells, thus inhibiting their infection to host cells. SARS-CoV RBD-specific antibodies could cross- react with SARS-CoV-2 RBD protein, and SARS-CoV RBD-induced antisera could cross-neutralize SARS-CoV-2, suggesting the potential to develop SARS-CoV RBD-based vaccines for prevention of SARS-CoV-2 and SARS-CoV infection.

2019 novel coronavirus, SARS-CoV-2, spike protein, receptor-binding domain, viral inhibitor, cross-neutralization

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17/03/2020 Correspondence
The proximal origin of SARS-CoV-2

Springer Nature

Authors
Kristian G. Andersen, Andrew Rambaut, W. Ian Lipkin, Edward C. Holmes, Robert F. Garry

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09/03/2020 Articles
Genomic diversity of SARS-CoV-2 in Coronavirus Disease 2019 patients

Oxford Academy

Authors
Zijie Shen, Yan Xiao, Lu Kang, Wentai Ma, Leisheng Shi, Li Zhang, Zhuo Zhou, Jing Yang, Jiaxin Zhong, Donghong Yang, Li Guo, Guoliang Zhang, Hongru Li, Yu Xu, Mingwei Chen, Zhancheng Gao, Jianwei Wang , Lili Ren, Mingkun Li

Background
A novel coronavirus (SARS-CoV-2) has infected more than 75,000 individuals and spread to over 20 countries. It is still unclear how fast the virus evolved and how the virus interacts with other microorganisms in the lung.

Methods
We have conducted metatranscriptome sequencing for the bronchoalveolar lavage fluid of eight SARS-CoV-2 patients, 25 community-acquired pneumonia (CAP) patients, and 20 healthy controls.

Results
The median number of intra-host variants was 1-4 in SARS-CoV-2 infected patients, which ranged between 0 and 51 in different samples. The distribution of variants on genes was similar to those observed in the population data (110 sequences). However, very few intra-host variants were observed in the population as polymorphism, implying either a bottleneck or purifying selection involved in the transmission of the virus, or a consequence of the limited diversity represented in the current polymorphism data. Although current evidence did not support the transmission of intra-host variants in a person-to-person spread, the risk should not be overlooked. The microbiota in SARS-CoV-2 infected patients was similar to those in CAP, either dominated by the pathogens or with elevated levels of oral and upper respiratory commensal bacteria.

Conclusion
SARS-CoV-2 evolves in vivo after infection, which may affect its virulence, infectivity, and transmissibility. Although how the intra-host variant spreads in the population is still elusive, it is necessary to strengthen the surveillance of the viral evolution in the population and associated clinical changes.

SARS-CoV-2, COVID-19, intra-host variant, microbiota, transmission

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05/03/2020 Correspondence
A distinct name is needed for the new coronavirus

The Lancet

Authors
Shibo Jiang, Zhengli Shi, Yuelong Shu, Jingdong Song, George F Gao, Wenjie Tan, Deyin Guo

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01/03/2020 Correspondence
Coordination of recovery and remap cap

REMAP-CAP

Authors
REMAP-CAP

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25/02/2020 Short Communication
Early phylogenetic estimate of the effective reproduction number of SA...

Early phylogenetic estimate of the effective reproduction number of SARS‐CoV‐2

Wiley Online Library

Authors
Alessia Lai, Annalisa Bergna, Carla Acciarri, Massimo Galli, Gianguglielmo Zehender

To reconstruct the evolutionary dynamics of the 2019 novel‐coronavirus recently causing an outbreak in Wuhan, China, 52 SARS‐CoV‐2 genomes available on 4 February 2020 at Global Initiative on Sharing All Influenza Data were analyzed. The two models used to estimate the reproduction number (coalescent‐based exponential growth and a birth‐death skyline method) indicated an estimated mean evolutionary rate of 7.8 × 10−4 subs/site/year (range, 1.1 × 10−4‐15 × 10−4) and a mean tMRCA of the tree root of 73 days. The estimated R value was 2.6 (range, 2.1‐5.1), and increased from 0.8 to 2.4 in December 2019. The estimated mean doubling time of the epidemic was between 3.6 and 4.1 days. This study proves the usefulness of phylogeny in supporting the surveillance of emerging new infections even as the epidemic is growing.

evolutionary dynamics, reproductive number, SARS‐CoV‐2

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24/02/2020 Articles
Functional assessment of cell entry and receptor usage for SARS-CoV-2....

Functional assessment of cell entry and receptor usage for SARS-CoV-2....

Nature Research

Authors
Michael Letko, Andrea Marzi, Vincent Munster

Abstract

Over the past 20 years, several coronaviruses have crossed the species barrier into humans, causing outbreaks of severe, and often fatal, respiratory illness. Since SARS-CoV was first identified in animal markets, global viromics projects have discovered thousands of coronavirus sequences in diverse animals and geographic regions. Unfortunately, there are few tools available to functionally test these viruses for their ability to infect humans, which has severely hampered efforts to predict the next zoo- notic viral outbreak. Here, we developed an approach to rapidly screen lineage B betacoronaviruses, such as SARS-CoV and the recent SARS-CoV-2, for receptor usage and their ability to infect cell types from different species. We show that host protease processing during viral entry is a significant barrier for several lineage B viruses and that bypassing this barrier allows several lineage B viruses to enter human cells through an unknown receptor. We also demonstrate how different lineage B viruses can recombine to gain entry into human cells, and confirm that human ACE2 is the receptor for the recently emerging SARS-CoV-2.

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19/02/2020 Viewpoint
Defining the Epidemiology of Covid-19 — Studies Needed

The NEW ENGLAND JOURNAL of MEDICINE

Authors
Marc Lipsitch, D.Phil., David L. Swerdlow, and Lyn Finelli

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19/02/2020 Letter
SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patie...

SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Lirong Zou, et all

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19/02/2020 Editorial
Coronaviruses in animals and humans

The bmj

Authors
Lisa F P Ng, Julian A Hiscox

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18/02/2020 Reviews
2019 Novel coronavirus: where we are and what we know

SPRINGER LINK

Authors
Zhangkai J. Cheng, Jing Shan



ABSTRACT
There is a current worldwide outbreak of a new type of coronavirus (2019-nCoV), which originated from Wuhan in China and has now spread to 17 other countries. Governments are under increased pressure to stop the outbreak spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak sites and from laboratories supporting the investigation. This paper aggregates and consolidates the virology, epidemiology, clinical management strategies from both English and Chinese literature, official news channels, and other official government documents. In addition, by fitting the number of infections with a single-term exponential model, we report that the infection is spreading at an exponential rate, with a doubling period of 1.8 days.

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13/02/2020 Articles
No credible evidence supporting claims of the

Taylor and Francis Group

Authors
Shan-Lu Liu, Linda J. Saif, Susan R. Weiss &amp; Lishan Su

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03/02/2020 Articles
A pneumonia outbreak associated with a new coronavirus of probable bat...

A pneumonia outbreak associated with a new coronavirus of probable bat origin

Nature

Authors
Peng Zhou, Xing-Lou Yang, Xian-Guang Wang, Ben Hu, Lei Zhang, Wei Zhang, Hao-Rui Si, Yan Zhu, Bei Li, Chao-Lin Huang, Hui-Dong Chen, Jing Chen, Yun Luo, Hua Guo, Ren-Di Jiang, Mei-Qin Liu, Ying Chen, Xu-Rui Shen, Xi Wang, Xiao-Shuang Zheng, Kai Zhao, Quan-Jiao Chen, Fei Deng, Lin-Lin Liu, Bing Yan, Fa-Xian Zhan, Yan-Yi Wang, Geng-Fu Xiao, Zheng-Li Shi

Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats1–4
Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans5–7
Here we report the identifcation and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confrmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from fve patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fuid of a critically ill patient could be neutralized by sera from several patients. Notably, we confrmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.

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30/01/2020 Articles
Genomic characterisation and epidemiology of 2019 novel coronavirus: i...

Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

The Lancet

Authors
Prof Roujian Lu, Xiang Zhao, Juan Li, Peihua Niu, Bo Yang, Honglong Wu, Wenling Wang, Hao Song, Baoying Huang, Na Zhu, Yuhai Bi, Xuejun Ma, Prof Faxian Zhan, Liang Wang, Tao Hu, Hong Zhou, Prof Zhenhong Hu, Prof Weimin Zhou, Li Zhao, Jing Chen, Yao Meng, Ji Wang, Yang Lin, Jianying Yuan, Zhihao Xie, Jinmin Ma, William J Liu, Dayan Wang,Prof Wenbo Xu, Edward C Holmes, George F Gao, Guizhen Wu

Summary
Background
In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. 

Methods
We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus.

Findings
The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. Interpretation 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. 

Funding
National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.

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22/01/2020 Reviews
Emerging coronaviruses: Genome structure, replication, and pathogenesi...

Emerging coronaviruses: Genome structure, replication, and pathogenesis

WILEY ONLINE LIBRARY

Authors
Yu Chen, Qianyun Liu, Deyin Guo

ABSTRACT
The recent emergence of a novel coronavirus (2019‐nCoV), which is causing an outbreak of unusual viral pneumonia in patients in Wuhan, a central city in China, is another warning of the risk of CoVs posed to public health. In this minireview, we provide a brief introduction of the general features of CoVs and describe diseases caused by different CoVs in humans and animals. This review will help understand the biology and potential risk of CoVs that exist in richness in wildlife such as bats.

22/01/2020 Reviews
Emerging coronaviruses: Genome structure, replication, and pathogenesi...

Emerging coronaviruses: Genome structure, replication, and pathogenesis

WILEY ONLINE LIBRARY

Authors
Yu Chen, Qianyun Liu, Deyin Guo

ABSTRACT
The recent emergence of a novel coronavirus (2019‐nCoV), which is causing an outbreak of unusual viral pneumonia in patients in Wuhan, a central city in China, is another warning of the risk of CoVs posed to public health. In this minireview, we provide a brief introduction of the general features of CoVs and describe diseases caused by different CoVs in humans and animals. This review will help understand the biology and potential risk of CoVs that exist in richness in wildlife such as bats.

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10/12/2018 Reviews
Origin and evolution of pathogenic coronaviruses

Nature Reviews

Authors
Jie Cui, Fang Li, Zheng-Li Shi

Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are two highly transmissible and pathogenic viruses that emerged in humans at the beginning of the 21st century. Both viruses likely originated in bats, and genetically diverse coronaviruses that are related to SARS-CoV and MERS-CoV were discovered in bats worldwide. In this Review, we summarize the current knowledge on the origin and evolution of these two pathogenic coronaviruses and discuss their receptor usage; we also highlight the diversity and potential of spillover of bat-borne coronaviruses, as evidenced by the recent spillover of swine acute diarrhoea syndrome coronavirus (SADS-CoV) to pigs.

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