Structural changes in the SARS-CoV-2 spike E406W mutant escaping a clinical monoclonal antibody cocktail

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The SARS-CoV-2 receptor-binding domain (RBD) E406W mutation abrogates neutralization mediated by the REGEN-CoV therapeutic monoclonal antibody (mAb) COVID-19 cocktail and the cilgavimab (AZD1061) mAb. Here, we show that this residue substitution remodels the ACE2-binding site allosterically, thereby...

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Autores principales: Addetia, Amin, Park, Young-Jun, Starr, Tyler, Greaney, Allison J., Sprouse, Kaitlin R, Bowen, John E., Tiles, Sasha W., Van Voorhis, Wesley C., Bloom, Jesse D., Corti, Davide, Walls, Alexandra C., Veesler, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8811904/
https://www.ncbi.nlm.nih.gov/pubmed/35118471
http://dx.doi.org/10.1101/2022.01.21.477288
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author Addetia, Amin
Park, Young-Jun
Starr, Tyler
Greaney, Allison J.
Sprouse, Kaitlin R
Bowen, John E.
Tiles, Sasha W.
Van Voorhis, Wesley C.
Bloom, Jesse D.
Corti, Davide
Walls, Alexandra C.
Veesler, David
author_facet Addetia, Amin
Park, Young-Jun
Starr, Tyler
Greaney, Allison J.
Sprouse, Kaitlin R
Bowen, John E.
Tiles, Sasha W.
Van Voorhis, Wesley C.
Bloom, Jesse D.
Corti, Davide
Walls, Alexandra C.
Veesler, David
author_sort Addetia, Amin
collection PubMed
description The SARS-CoV-2 receptor-binding domain (RBD) E406W mutation abrogates neutralization mediated by the REGEN-CoV therapeutic monoclonal antibody (mAb) COVID-19 cocktail and the cilgavimab (AZD1061) mAb. Here, we show that this residue substitution remodels the ACE2-binding site allosterically, thereby dampening receptor recognition severely and altering the epitopes recognized by these three mAbs. Although vaccine-elicited neutralizing antibody titers are decreased similarly against the E406 mutant and the Delta or Epsilon variants, broadly neutralizing sarbecovirus mAbs, including a clinical mAb, inhibit the E406W spike mutant.
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spelling pubmed-88119042022-02-04 Structural changes in the SARS-CoV-2 spike E406W mutant escaping a clinical monoclonal antibody cocktail Addetia, Amin Park, Young-Jun Starr, Tyler Greaney, Allison J. Sprouse, Kaitlin R Bowen, John E. Tiles, Sasha W. Van Voorhis, Wesley C. Bloom, Jesse D. Corti, Davide Walls, Alexandra C. Veesler, David bioRxiv Article The SARS-CoV-2 receptor-binding domain (RBD) E406W mutation abrogates neutralization mediated by the REGEN-CoV therapeutic monoclonal antibody (mAb) COVID-19 cocktail and the cilgavimab (AZD1061) mAb. Here, we show that this residue substitution remodels the ACE2-binding site allosterically, thereby dampening receptor recognition severely and altering the epitopes recognized by these three mAbs. Although vaccine-elicited neutralizing antibody titers are decreased similarly against the E406 mutant and the Delta or Epsilon variants, broadly neutralizing sarbecovirus mAbs, including a clinical mAb, inhibit the E406W spike mutant. Cold Spring Harbor Laboratory 2022-01-25 /pmc/articles/PMC8811904/ /pubmed/35118471 http://dx.doi.org/10.1101/2022.01.21.477288 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Addetia, Amin
Park, Young-Jun
Starr, Tyler
Greaney, Allison J.
Sprouse, Kaitlin R
Bowen, John E.
Tiles, Sasha W.
Van Voorhis, Wesley C.
Bloom, Jesse D.
Corti, Davide
Walls, Alexandra C.
Veesler, David
Structural changes in the SARS-CoV-2 spike E406W mutant escaping a clinical monoclonal antibody cocktail
title Structural changes in the SARS-CoV-2 spike E406W mutant escaping a clinical monoclonal antibody cocktail
title_full Structural changes in the SARS-CoV-2 spike E406W mutant escaping a clinical monoclonal antibody cocktail
title_fullStr Structural changes in the SARS-CoV-2 spike E406W mutant escaping a clinical monoclonal antibody cocktail
title_full_unstemmed Structural changes in the SARS-CoV-2 spike E406W mutant escaping a clinical monoclonal antibody cocktail
title_short Structural changes in the SARS-CoV-2 spike E406W mutant escaping a clinical monoclonal antibody cocktail
title_sort structural changes in the sars-cov-2 spike e406w mutant escaping a clinical monoclonal antibody cocktail
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8811904/
https://www.ncbi.nlm.nih.gov/pubmed/35118471
http://dx.doi.org/10.1101/2022.01.21.477288
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