期刊
NATURE
卷 583, 期 7815, 页码 290-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41586-020-2349-y
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资金
- National Institute of General Medical Sciences [R01GM120553]
- National Institute of Allergy and Infectious Diseases [HHSN272201700059C, 75N93019C00062]
- Pew Biomedical Scholars Award
- Investigators in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund
- University of Washington Arnold and Mabel Beckman cryo-EM centre
- Pasteur Institute
- Department of Energy Office of Science User Facility [DE-AC02-05CH11231]
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 12 . 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 Sglycoprotein 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 antibodiesthat 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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