Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV 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 () and Davide Corti ()
Additional contact information
Dora Pinto: Vir Biotechnology
Young-Jun Park: University of Washington
Martina Beltramello: Vir Biotechnology
Alexandra C. Walls: University of Washington
M. Alejandra Tortorici: University of Washington
Siro Bianchi: Vir Biotechnology
Stefano Jaconi: Vir Biotechnology
Katja Culap: Vir Biotechnology
Fabrizia Zatta: Vir Biotechnology
Anna De Marco: Vir Biotechnology
Alessia Peter: Vir Biotechnology
Barbara Guarino: Vir Biotechnology
Roberto Spreafico: Vir Biotechnology
Elisabetta Cameroni: Vir Biotechnology
James Brett Case: Washington University School of Medicine
Rita E. Chen: Washington University School of Medicine
Colin Havenar-Daughton: Vir Biotechnology
Gyorgy Snell: Vir Biotechnology
Amalio Telenti: Vir Biotechnology
Herbert W. Virgin: Vir Biotechnology
Antonio Lanzavecchia: Vir Biotechnology
Michael S. Diamond: Washington University School of Medicine
Katja Fink: Vir Biotechnology
David Veesler: University of Washington
Davide Corti: Vir Biotechnology

Nature, 2020, vol. 583, issue 7815, 290-295

Abstract: Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged coronavirus that is responsible for the current pandemic of coronavirus disease 2019 (COVID-19), which has resulted in more than 3.7 million infections and 260,000 deaths as of 6 May 20201,2. 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 several monoclonal antibodies that target the S glycoprotein of SARS-CoV-2, which we identified from memory B cells of an individual who was infected with severe acute respiratory syndrome coronavirus (SARS-CoV) 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 receptor-binding domain of the S glycoprotein. Using cryo-electron microscopy and binding assays, we show that S309 recognizes an epitope containing a glycan that is conserved within the Sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails that include S309 in combination with other antibodies that we identified further enhanced SARS-CoV-2 neutralization, and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309 and antibody cocktails containing S309 for prophylaxis in individuals at a high risk of exposure or as a post-exposure therapy to limit or treat severe disease.

Date: 2020
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DOI: 10.1038/s41586-020-2349-y

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