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- Matthew McCallum
- Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
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- Nadine Czudnochowski
- Vir Biotechnology, San Francisco, CA 94158, USA.
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- Laura E. Rosen
- Vir Biotechnology, San Francisco, CA 94158, USA.
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- Samantha K. Zepeda
- Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
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- John E. Bowen
- Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
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- Alexandra C. Walls
- Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
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- Kevin Hauser
- Vir Biotechnology, San Francisco, CA 94158, USA.
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- Anshu Joshi
- Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
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- Cameron Stewart
- Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
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- Josh R. Dillen
- Vir Biotechnology, San Francisco, CA 94158, USA.
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- Abigail E. Powell
- Vir Biotechnology, San Francisco, CA 94158, USA.
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- Tristan I. Croll
- Cambridge Institute for Medical Research, Department of Haematology, University of Cambridge, Cambridge, UK.
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- Jay Nix
- Molecular Biology Consortium, Advanced Light Source, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
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- Herbert W. Virgin
- Vir Biotechnology, San Francisco, CA 94158, USA.
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- Davide Corti
- Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.
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- Gyorgy Snell
- Vir Biotechnology, San Francisco, CA 94158, USA.
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- David Veesler
- Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
抄録
<jats:p>The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern evades antibody-mediated immunity that comes from vaccination or infection with earlier variants due to accumulation of numerous spike mutations. To understand the Omicron antigenic shift, we determined cryo–electron microscopy and x-ray crystal structures of the spike protein and the receptor-binding domain bound to the broadly neutralizing sarbecovirus monoclonal antibody (mAb) S309 (the parent mAb of sotrovimab) and to the human ACE2 receptor. We provide a blueprint for understanding the marked reduction of binding of other therapeutic mAbs that leads to dampened neutralizing activity. Remodeling of interactions between the Omicron receptor-binding domain and human ACE2 likely explains the enhanced affinity for the host receptor relative to the ancestral virus.</jats:p>
収録刊行物
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- Science
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Science 375 (6583), 864-868, 2022-02-25
American Association for the Advancement of Science (AAAS)