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

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 c...

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Autores principales: Starr, Tyler N., Greaney, Allison J., Addetia, Amin, Hannon, William W., Choudhary, Manish C., Dingens, Adam S., Li, Jonathan Z., Bloom, Jesse D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963219/
https://www.ncbi.nlm.nih.gov/pubmed/33495308
http://dx.doi.org/10.1126/science.abf9302
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author Starr, Tyler N.
Greaney, Allison J.
Addetia, Amin
Hannon, William W.
Choudhary, Manish C.
Dingens, Adam S.
Li, Jonathan Z.
Bloom, Jesse D.
author_facet Starr, Tyler N.
Greaney, Allison J.
Addetia, Amin
Hannon, William W.
Choudhary, Manish C.
Dingens, Adam S.
Li, Jonathan Z.
Bloom, Jesse D.
author_sort Starr, Tyler N.
collection PubMed
description 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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spelling pubmed-79632192021-03-24 Prospective mapping of viral mutations that escape antibodies used to treat COVID-19 Starr, Tyler N. Greaney, Allison J. Addetia, Amin Hannon, William W. Choudhary, Manish C. Dingens, Adam S. Li, Jonathan Z. Bloom, Jesse D. Science Reports 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. American Association for the Advancement of Science 2021-02-19 2021-01-25 /pmc/articles/PMC7963219/ /pubmed/33495308 http://dx.doi.org/10.1126/science.abf9302 Text en 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 (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Reports
Starr, Tyler N.
Greaney, Allison J.
Addetia, Amin
Hannon, William W.
Choudhary, Manish C.
Dingens, Adam S.
Li, Jonathan Z.
Bloom, Jesse D.
Prospective mapping of viral mutations that escape antibodies used to treat COVID-19
title Prospective mapping of viral mutations that escape antibodies used to treat COVID-19
title_full Prospective mapping of viral mutations that escape antibodies used to treat COVID-19
title_fullStr Prospective mapping of viral mutations that escape antibodies used to treat COVID-19
title_full_unstemmed Prospective mapping of viral mutations that escape antibodies used to treat COVID-19
title_short Prospective mapping of viral mutations that escape antibodies used to treat COVID-19
title_sort prospective mapping of viral mutations that escape antibodies used to treat covid-19
topic Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963219/
https://www.ncbi.nlm.nih.gov/pubmed/33495308
http://dx.doi.org/10.1126/science.abf9302
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