Journal
NATURE
Volume 584, Issue 7819, Pages 115-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41586-020-2380-z
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Funding
- Bill & Melinda Gates Foundation
- Science and Technology Innovation Committee of Shenzhen Municipality [202002073000002]
- Tsinghua University Initiative Scientific Research Program [20201080053]
- National Beijing Municipal Science and Technology Commission [171100000517-001, 171100000517-003]
- Beijing Advanced Innovation Center for Structural Biology at Tsinghua University
- National Key Plan for Scientific Research and Development of China [2016YFD0500307]
- Tencent Foundation
- Shuidi Foundation
- TH Capital
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The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a global health emergency that is in urgent need of intervention(1-3). The entry of SARS-CoV-2 into its target cells depends on binding between the receptor-binding domain (RBD) of the viral spike protein and its cellular receptor, angiotensin-converting enzyme 2 (ACE2)(2,4-6). Here we report the isolation and characterization of 206 RBD-specific monoclonal antibodies derived from single B cells from 8 individuals infected with SARS-CoV-2. We identified antibodies that potently neutralize SARS-CoV-2; this activity correlates with competition with ACE2 for binding to RBD. Unexpectedly, the anti-SARS-CoV-2 antibodies and the infected plasma did not cross-react with the RBDs of SARS-CoV or Middle East respiratory syndrome-related coronavirus (MERS-CoV), although there was substantial plasma cross-reactivity to their trimeric spike proteins. Analysis of the crystal structure of RBD-bound antibody revealed that steric hindrance inhibits viral engagement with ACE2, thereby blocking viral entry. These findings suggest that anti-RBD antibodies are largely viral-species-specific inhibitors. The antibodies identified here may be candidates for development of clinical interventions against SARS-CoV-2. In a study of antibodies isolated from patients infected with SARS-CoV-2, antibodies that potently neutralized the virus competed with angiotensin-converting enzyme 2 for binding to the receptor-binding domain of the viral spike protein, suggesting that antibodies that disrupt this interaction could be developed to treat SARS-CoV-2 infection.
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