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

Authors: Amin Addetia; Amin Addetia; Tyler N. Starr; Allison J. Greaney; Allison J. Greaney; Jonathan Z. Li; Manish Chandra Choudhary; +6 Authors

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

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-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.

Keywords

Multidisciplinary, SARS-CoV-2, Immunization, Passive, COVID-19, Antibodies, Monoclonal, Humanized, Antibodies, Viral, Article, Drug Combinations, Amino Acid Substitution, Protein Domains, Mutation, Spike Glycoprotein, Coronavirus, Humans, Angiotensin-Converting Enzyme 2, Cells, Cultured, COVID-19 Serotherapy, Reports, Protein Binding, Receptors, Coronavirus

  • BIP!
    Impact byBIP!
    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    706
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 0.01%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 1%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 0.01%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
706
Top 0.01%
Top 1%
Top 0.01%
Green
hybrid