Structural and functional analysis of a potent sarbecovirus neutralizing antibody
Alexandra C. Walls,
M. Alejandra Tortorici,
Anna De Marco,
James Brett Case,
Rita E. Chen,
Herbert W. Virgin,
Michael S. Diamond,
Posted 09 Apr 2020
bioRxiv DOI: 10.1101/2020.04.07.023903 (published DOI: 10.1038/s41586-020-2349-y)
Posted 09 Apr 2020
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 deaths,. 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. : #ref-1 : #ref-2
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