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

By Tyler N. Starr, Allison J. Greaney, Amin Addetia, William H. Hannon, Manish C. Choudhary, Adam S. Dingens, Jonathan Z Li, Jesse Bloom

Posted 01 Dec 2020
bioRxiv DOI: 10.1101/2020.11.30.405472

Antibodies are becoming a frontline therapy for SARS-CoV-2, but the risk of viral evolutionary escape remains unclear. Here we map how all mutations to SARS-CoV-2's receptor-binding domain (RBD) affect binding by the antibodies in Regeneron's REGN-COV2 cocktail and Eli Lilly's LY-CoV016. These complete maps uncover a single amino-acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2, as well as in lab viral escape selections. Finally, the maps reveal that mutations escaping each individual antibody are already present in circulating SARS-CoV-2 strains. Overall, these complete escape maps enable immediate interpretation of the consequences of mutations observed during viral surveillance.

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