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

ABSTRACT: 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.

SUBMITTER: Addetia A

PROVIDER: S-EPMC8811904 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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

Addetia Amin A Park Young-Jun YJ Starr Tyler T Greaney Allison J AJ Sprouse Kaitlin R KR Bowen John E JE Tiles Sasha W SW Van Voorhis Wesley C WC Bloom Jesse D JD Corti Davide D Walls Alexandra C AC Veesler David D

bioRxiv : the preprint server for biology 20220125

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 mutan ...[more]

PMID: 35118471

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

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Successful Clearance of 300 Day SARS-CoV-2 Infection in a Subject with B-Cell Depletion Associated Prolonged (B-DEAP) COVID by REGEN-COV Anti-Spike Monoclonal Antibody Cocktail.

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| S-EPMC8310246 | biostudies-literature

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