Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody
Date
2020-05-18Author
Pinto, Dora
Park, Young Jun
Beltramello, Martina
Walls, Alexandra C.
Tortorici, M. Alejandra
Bianchi, Siro
Jaconi, Stefano
Culap, Katja
Zatta, Fabrizia
De Marco, Anna
Peter, Alessia
Guarino, Barbara
Spreafico, Roberto
Cameroni, Elisabetta
Case, James Brett
Chen, Rita E.
Havenar-Daughton, Colin
Snell, Gyorgy
Telenti, Amalio
Virgin, Herbert W.
Lanzavecchia, Antonio
Diamond, Michael S.
Fink, Katja
Veesler, David
Corti, Davide
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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.
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https://www.nature.com/articles/s41586-020-2349-yCollections
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