Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Structural and functional analysis of a potent sarbecovirus neutralizing antibody

View ORCID ProfileDora Pinto, Young-Jun Park, View ORCID ProfileMartina Beltramello, Alexandra C. Walls, M. Alejandra Tortorici, Siro Bianchi, View ORCID ProfileStefano Jaconi, Katja Culap, Fabrizia Zatta, Anna De Marco, Alessia Peter, View ORCID ProfileBarbara Guarino, View ORCID ProfileRoberto Spreafico, View ORCID ProfileElisabetta Cameroni, James Brett Case, Rita E. Chen, View ORCID ProfileColin Havenar-Daughton, Gyorgy Snell, View ORCID ProfileAmalio Telenti, View ORCID ProfileHerbert W. Virgin, View ORCID ProfileAntonio Lanzavecchia, Michael S. Diamond, View ORCID ProfileKatja Fink, View ORCID ProfileDavid Veesler, View ORCID ProfileDavide Corti
doi: https://doi.org/10.1101/2020.04.07.023903
Dora Pinto
1Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Dora Pinto
Young-Jun Park
2Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Martina Beltramello
1Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Martina Beltramello
Alexandra C. Walls
2Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M. Alejandra Tortorici
2Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA
3Institut Pasteur & CNRS UMR 3569, Unité de Virologie Structurale, 75015, Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Siro Bianchi
1Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stefano Jaconi
1Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Stefano Jaconi
Katja Culap
1Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Fabrizia Zatta
1Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anna De Marco
1Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alessia Peter
1Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Barbara Guarino
1Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Barbara Guarino
Roberto Spreafico
4Vir Biotechnology, San Francisco, California 94158, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Roberto Spreafico
Elisabetta Cameroni
1Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Elisabetta Cameroni
James Brett Case
6Departments of Medicine, Molecular Microbiology, Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 631110, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rita E. Chen
6Departments of Medicine, Molecular Microbiology, Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 631110, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Colin Havenar-Daughton
4Vir Biotechnology, San Francisco, California 94158, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Colin Havenar-Daughton
Gyorgy Snell
4Vir Biotechnology, San Francisco, California 94158, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Amalio Telenti
4Vir Biotechnology, San Francisco, California 94158, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Amalio Telenti
Herbert W. Virgin
4Vir Biotechnology, San Francisco, California 94158, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Herbert W. Virgin
Antonio Lanzavecchia
1Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
5Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Antonio Lanzavecchia
Michael S. Diamond
6Departments of Medicine, Molecular Microbiology, Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 631110, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Katja Fink
1Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Katja Fink
David Veesler
2Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for David Veesler
  • For correspondence: dveesler@uw.edu dcorti@vir.bio
Davide Corti
1Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Davide Corti
  • For correspondence: dveesler@uw.edu dcorti@vir.bio
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

SARS-CoV-2 is a newly emerged coronavirus responsible for the current COVID-19 pandemic that has resulted in more than one million infections and 73,000 deaths1,2. Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here we describe multiple monoclonal antibodies targeting SARS-CoV-2 S identified from memory B cells of a SARS survivor infected in 2003. One antibody, named S309, potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 by engaging the S receptor-binding domain. Using cryo-electron microscopy and binding assays, we show that S309 recognizes a glycan-containing epitope that is conserved within the sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails including S309 along with other antibodies identified here further enhanced SARS-CoV-2 neutralization and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309 and S309-containing antibody cocktails for prophylaxis in individuals at high risk of exposure or as a post-exposure therapy to limit or treat severe disease.

Competing Interest Statement

D.P., S.B., K.C., E.C., C.H-D., G.S., M.B., A.K., K.F., A.P. F.Z., S.J., B.G., A.D.M., A.L., A.T., H.W.V, R.S. and D.C. are employees of Vir Biotechnology Inc. and may hold shares in Vir Biotechnology Inc. M.S.D. is a consultant for Inbios, Eli Lilly, Vir Biotechnology, NGM Biopharmaceuticals, and Emergent BioSolutions and on the Scientific Advisory Board of Moderna. The Diamond laboratory at Washington University School of Medicine has received sponsored research agreements from Moderna. The other authors declare no competing financial interests.

Footnotes

  • Order of authors in the webpage. Davide Corti name was put as first but it should be last, co-corresponding with David Veesler

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted April 09, 2020.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Structural and functional analysis of a potent sarbecovirus neutralizing antibody
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Structural and functional analysis of a potent sarbecovirus neutralizing antibody
Dora Pinto, Young-Jun Park, Martina Beltramello, Alexandra C. Walls, M. Alejandra Tortorici, Siro Bianchi, Stefano Jaconi, Katja Culap, Fabrizia Zatta, Anna De Marco, Alessia Peter, Barbara Guarino, Roberto Spreafico, Elisabetta Cameroni, James Brett Case, Rita E. Chen, Colin Havenar-Daughton, Gyorgy Snell, Amalio Telenti, Herbert W. Virgin, Antonio Lanzavecchia, Michael S. Diamond, Katja Fink, David Veesler, Davide Corti
bioRxiv 2020.04.07.023903; doi: https://doi.org/10.1101/2020.04.07.023903
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Structural and functional analysis of a potent sarbecovirus neutralizing antibody
Dora Pinto, Young-Jun Park, Martina Beltramello, Alexandra C. Walls, M. Alejandra Tortorici, Siro Bianchi, Stefano Jaconi, Katja Culap, Fabrizia Zatta, Anna De Marco, Alessia Peter, Barbara Guarino, Roberto Spreafico, Elisabetta Cameroni, James Brett Case, Rita E. Chen, Colin Havenar-Daughton, Gyorgy Snell, Amalio Telenti, Herbert W. Virgin, Antonio Lanzavecchia, Michael S. Diamond, Katja Fink, David Veesler, Davide Corti
bioRxiv 2020.04.07.023903; doi: https://doi.org/10.1101/2020.04.07.023903

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Immunology
Subject Areas
All Articles
  • Animal Behavior and Cognition (3606)
  • Biochemistry (7575)
  • Bioengineering (5529)
  • Bioinformatics (20806)
  • Biophysics (10333)
  • Cancer Biology (7986)
  • Cell Biology (11644)
  • Clinical Trials (138)
  • Developmental Biology (6610)
  • Ecology (10214)
  • Epidemiology (2065)
  • Evolutionary Biology (13623)
  • Genetics (9543)
  • Genomics (12851)
  • Immunology (7923)
  • Microbiology (19551)
  • Molecular Biology (7666)
  • Neuroscience (42127)
  • Paleontology (308)
  • Pathology (1258)
  • Pharmacology and Toxicology (2203)
  • Physiology (3268)
  • Plant Biology (7044)
  • Scientific Communication and Education (1294)
  • Synthetic Biology (1951)
  • Systems Biology (5427)
  • Zoology (1118)