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

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.

Afiliación

Addetia A; Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, Washington, USA.
Park YJ; Department of Biochemistry, University of Washington, Seattle, Washington, USA.
Starr T; Department of Biochemistry, University of Washington, Seattle, Washington, USA.
Greaney AJ; Howard Hughes Medical Institute, Seattle, WA 98195, USA.
Sprouse KR; Howard Hughes Medical Institute, Seattle, WA 98195, USA.
Bowen JE; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Tiles SW; Howard Hughes Medical Institute, Seattle, WA 98195, USA.
Van Voorhis WC; Department of Biochemistry, University of Washington, Seattle, Washington, USA.
Bloom JD; Department of Biochemistry, University of Washington, Seattle, Washington, USA.
Corti D; Center for Emerging and Re-emerging Infectious Diseases, Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.
Walls AC; Center for Emerging and Re-emerging Infectious Diseases, Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.
Veesler D; Howard Hughes Medical Institute, Seattle, WA 98195, USA.

bioRxiv ; 2022 Jan 25.

Article en En | MEDLINE | ID: mdl-35118471

ABSTRACT

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.

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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos

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