Prospective mapping of viral mutations that escape antibodies used to treat COVID-19
Top Cited Papers
Open Access
- 18 February 2021
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 371 (6531), 850-+
- https://doi.org/10.1126/science.abf9302
Abstract
Antibodies are a potential therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the risk of the virus evolving to escape them remains unclear. Here we map how all mutations to the receptor binding domain (RBD) of SARS-CoV-2 affect binding by the antibodies in the REGN-COV2 cocktail and the antibody LY-CoV016. These complete maps uncover a single amino acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies, REGN10933 and REGN10987, targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2 and during in vitro viral escape selections. Finally, the maps reveal that mutations escaping the individual antibodies are already present in circulating SARS-CoV-2 strains. These complete escape maps enable interpretation of the consequences of mutations observed during viral surveillance.Funding Information
- Howard Hughes Medical Institute (Investigator)
- Howard Hughes Medical Institute (Investigator)
- National Institute of Allergy and Infectious Diseases (R01AI127893)
- National Institute of Allergy and Infectious Diseases (R01AI141707)
- Bill and Melinda Gates Foundation (INV-004949)
- Damon Runyon Cancer Research Foundation (DRG-2381-19)
- Massachusetts Consortium for Pathogen Readiness
- Washington Research Foundation (Innovation Fellow)
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