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

TN Starr, AJ Greaney, A Addetia, WW Hannon… - Science, 2021 - science.org
Science, 2021science.org
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 …
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.
AAAS