Structural and functional analysis of a potent sarbecovirus neutralizing antibody
Open accessPreprint — published as 10.1038/s41586-020-2349-y · Paper page
Abstract
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 1,2 . 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.
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Protection against SARS-CoV-2 is thought to be mediated by neutralizing antibodies against the S protein.
“Protection is thought to be mediated by neutralizing antibodies against the S protein (7, 8)”
From An <i>Alphavirus</i> -derived replicon RNA vaccine induces SARS-CoV-2 neutralizing antibody and T cell responses in mice and nonhuman primates (2020) · cites this paper as [8]
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- Authors
- Pinto, D., Park, Y.-J., Beltramello, M., Walls, A. C., Tortorici, M. A., Bianchi, S., Jaconi, S., Culap, K., Zatta, F., De Marco, A., Peter, A., Guarino, B., Spreafico, R., Cameroni, E., Case, J. B., Chen, R. E., Havenar-Daughton, C., Snell, G., Telenti, A., Virgin, H. W., Lanzavecchia, A., Diamond, M. S., Fink, K., Veesler, D., & Corti, D.
- Affiliations
- Vir Biotechnology (Switzerland) (CH)
- University of Washington (US)
- Centre National de la Recherche Scientifique (FR)
- VIR Biotechnology (United States) (US)
- Washington University in St. Louis (US)
- Corresponding author
- Veesler, David
- Corti, Davide
- ORCID
- Pinto, Dora
- Park, Young-Jun
- Beltramello, Martina
- Walls, Alexandra C.
- Tortorici, M. Alejandra
- Bianchi, Siro
- Jaconi, Stefano
- Culap, Katja
- Zatta, Fabrizia
- De Marco, Anna
- Peter, Alessia
- Guarino, Barbara
- Spreafico, Roberto
- Cameroni, Elisabetta
- Case, James Brett
- Chen, Rita E.
- Havenar-Daughton, Colin
- Snell, Gyorgy
- Telenti, Amalio
- Virgin, Herbert W.
- Lanzavecchia, Antonio
- Diamond, Michael S.
- Fink, Katja
- Veesler, David
- Corti, Davide
- Venue
- Nature
- Publisher
- openRxiv
- Published
- 2020-04-09
- Volume
- 583
- Issue
- 7815
- Pages
- 290-295
- ISSN
- 0028-0836 (ISSN-L)
- OpenAlex
- W3025744748
- Cited by
- 1,752
- References
- 0
- Citations by year
- 2026: 68 · 2025: 121 · 2024: 173 · 2023: 213 · 2022: 376 · 2021: 526 · 2020: 273
- FWCI
- 44.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- U.S. Department of Energy (-AC02-05CH11231, Contract No. DE-AC02-05-CH11231, 05CH11231, No. DE-AC02-05-CH11231, DE AC02 05CH11231, DE-AC02-)
- Burroughs Wellcome Fund (DE-AC02-05CH11231)
- University of Washington
- National Institutes of Health (1s10od023476-01)
- Office of Science (No. DE-AC02- 05-CH11231, DEAC02–05CH11231, AC02-05CH11231, DE-AC02, Contract No. DE-AC02-05CH11231)
- National Institute of General Medical Sciences (DE-AC02-05CH11231, R01GM120553)
- National Institute of Allergy and Infectious Diseases (HHSN272201700059C, 75N93019C00062)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- SARS-CoV-2, COVID-19 pandemic, monoclonal antibodies, spike protein, receptor binding domain, cross-neutralization, SARS-CoV, memory B cells, antibody cocktail, neutralization escape mutants, post-exposure prophylaxis, therapeutic antibodies, carbohydrate epitopes
- MeSH terms
- Betacoronavirus, Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, Animals, Antibodies, Monoclonal, Antibodies, Viral, Antibody-Dependent Cell Cytotoxicity, B-Lymphocytes, Chlorocebus aethiops, Cross Reactions, Humans, Immunoglobulin Fab Fragments, Immunologic Memory, Killer Cells, Natural, Peptidyl-Dipeptidase A, Models, Molecular, Neutralization Tests, Pneumonia, Viral, Vero Cells, Coronavirus Infections, Epitopes, B-Lymphocyte, Cryoelectron Microscopy, Severe Acute Respiratory Syndrome, Severe acute respiratory syndrome-related coronavirus, Immune Evasion, Antibodies, Neutralizing, HEK293 Cells, Pandemics, Spike Glycoprotein, Coronavirus
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