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bioRxiv · 10.1101/2020.11.30.405472

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

Starr, T. N.·Greaney, A. J.·Addetia, A.·Hannon, W. H.·Choudhary, M. C.·Dingens, A. S.·Li, J. Z.·Bloom, J. D.
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Abstract

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-2s receptor-binding domain (RBD) affect binding by the antibodies in Regenerons REGN-COV2 cocktail and Eli Lillys 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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Starr, T. N., Greaney, A. J., Addetia, A., Hannon, W. H., Choudhary, M. C., Dingens, A. S., Li, J. Z., Bloom, J. D.. 2020-12-01. Prospective mapping of viral mutations that escape antibodies used to treat COVID-19. https://doi.org/10.1101/2020.11.30.405472

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