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

Amin Addetia; Young-Jun Park; Tyler Starr; Allison J. Greaney; Kaitlin R. Sprouse; John E. Bowen; Sasha W. Tiles; Wesley C. Van Voorhis; Jesse D. Bloom; Davide Corti; Alexandra C. Walls; David Veesler

Cell Reports (Jun 2023)

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

Amin Addetia,
Young-Jun Park,
Tyler Starr,
Allison J. Greaney,
Kaitlin R. Sprouse,
John E. Bowen,
Sasha W. Tiles,
Wesley C. Van Voorhis,
Jesse D. Bloom,
Davide Corti,
Alexandra C. Walls,
David Veesler

Affiliations

Amin Addetia: Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA, USA; Department of Biochemistry, University of Washington, Seattle, WA, USA
Young-Jun Park: Department of Biochemistry, University of Washington, Seattle, WA, USA; Howard Hughes Medical Institute, Seattle, WA 98195, USA
Tyler Starr: Howard Hughes Medical Institute, Seattle, WA 98195, USA; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Allison J. Greaney: Howard Hughes Medical Institute, Seattle, WA 98195, USA
Kaitlin R. Sprouse: Department of Biochemistry, University of Washington, Seattle, WA, USA
John E. Bowen: Department of Biochemistry, University of Washington, Seattle, WA, USA
Sasha W. Tiles: 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
Wesley C. Van Voorhis: 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
Jesse D. Bloom: Howard Hughes Medical Institute, Seattle, WA 98195, USA; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Davide Corti: Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
Alexandra C. Walls: Department of Biochemistry, University of Washington, Seattle, WA, USA; Howard Hughes Medical Institute, Seattle, WA 98195, USA
David Veesler: Department of Biochemistry, University of Washington, Seattle, WA, USA; Howard Hughes Medical Institute, Seattle, WA 98195, USA; Corresponding author

Journal volume & issue: Vol. 42, no. 6
p. 112621

Abstract

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Summary: Continued evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is eroding antibody responses elicited by prior vaccination and infection. 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 AZD1061 (COV2-2130) mAb. Here, we show that this mutation remodels the receptor-binding site allosterically, thereby altering the epitopes recognized by these three mAbs and vaccine-elicited neutralizing antibodies while remaining functional. Our results demonstrate the spectacular structural and functional plasticity of the SARS-CoV-2 RBD, which is continuously evolving in emerging SARS-CoV-2 variants, including currently circulating strains that are accumulating mutations in the antigenic sites remodeled by the E406W substitution.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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