[HTML][HTML] Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody

D Pinto, YJ Park, M Beltramello, AC Walls, MA Tortorici… - Nature, 2020 - nature.com
D Pinto, YJ Park, M Beltramello, AC Walls, MA Tortorici, S Bianchi, S Jaconi, K Culap, F Zatta…
Nature, 2020nature.com
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 2020,. 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 …
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 2020,. 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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