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

Type Journal Article Author Tyler N. Starr Author Allison J. Greaney Author Amin Addetia Author William W. Hannon Author Manish C. Choudhary Author Adam S. Dingens Author Jonathan Z. Li Author Jesse D. Bloom URL https://science.sciencemag.org/content/371/6531/850 Rights Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Volume 371 Issue 6531 Pages 850-854 Publication Science ISSN 0036-8075, 1095-9203 Date 19/02/2021 Extra Publisher: American Association for the Advancement of Science Section: Report PMID: 33495308 DOI 10.1126/science.abf9302 Library Catalog science.sciencemag.org Language en Abstract Mapping antibody escape in SARS-CoV-2 Several antibodies are in use or under development as therapies to treat COVID-19. As new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants emerge, it is important to predict whether they will remain susceptible to antibody treatment. Starr et al. used a yeast library that covers all mutations to the SARS-CoV-2 receptor-binding domain that do not strongly disrupt binding to the host receptor (ACE2) and mapped how these mutations affect binding to three leading anti–SARS-CoV-2 antibodies. The maps identify mutations that escape antibody binding, including a single mutation that escapes both antibodies in the Regeneron antibody cocktail. Many of the mutations that escape single antibodies are circulating in the human population. Science, this issue p. 850 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. Complete maps of SARS-CoV-2 mutations that escape the Regeneron monoclonal antibody cocktail help explain viral evolution in a treated patient. Complete maps of SARS-CoV-2 mutations that escape the Regeneron monoclonal antibody cocktail help explain viral evolution in a treated patient.