期刊
SCIENCE
卷 370, 期 6519, 页码 950-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abe3354
关键词
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资金
- National Institute of General Medical Sciences [R01GM120553]
- National Institute of Allergy and Infectious Diseases [HHSN272201700059C]
- Pew Biomedical Scholars Award
- Investigators in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund
- Fast Grants
- University of Washington Arnold and Mabel Beckman cryoEM center
- Pasteur Institute
- KU Leuven/UZ Leuven COVID-19 Fund
- Flanders Fonds voor Wetenschappelijk Onderzoek (FWO) [G0G4820N]
- Bill and Melinda Gates Foundation [INV-006366]
- Bill and Melinda Gates Foundation [INV-006366] Funding Source: Bill and Melinda Gates Foundation
Efficient therapeutic options are needed to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has caused more than 922,000 fatalities as of 13 September 2020. We report the isolation and characterization of two ultrapotent SARS-CoV-2 human neutralizing antibodies (S2E12 and S2M11) that protect hamsters against SARS-CoV-2 challenge. Cryo-electron microscopy structures show that S2E12 and S2M11 competitively block angiotensin-converting enzyme 2 (ACE2) attachment and that S2M11 also locks the spike in a closed conformation by recognition of a quaternary epitope spanning two adjacent receptor-binding domains. Antibody cocktails that include S2M11, S2E12, or the previously identified S309 antibody broadly neutralize a panel of circulating SARS-CoV-2 isolates and activate effector functions. Our results pave the way to implement antibody cocktails for prophylaxis or therapy, circumventing or limiting the emergence of viral escape mutants.
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