4.8 Article

Prospective mapping of viral mutations that escape antibodies used to treat COVID-19

期刊

SCIENCE
卷 371, 期 6531, 页码 850-+

出版社

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abf9302

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资金

  1. NIAID [R01AI127893, R01AI141707, T32AI083203]
  2. Gates Foundation [INV-004949]
  3. Massachusetts Consortium for Pathogen Readiness
  4. ORIP [S10OD028685]
  5. Bill and Melinda Gates Foundation [INV-004949] Funding Source: Bill and Melinda Gates Foundation

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Research has found that mutations in the receptor binding domain (RBD) of SARS-CoV-2 may potentially escape the action of the REGN-COV2 cocktail, providing important information for interpreting mutations observed during viral surveillance.
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.

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