Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement

McCallum, Matthew; Czudnochowski, Nadine; Rosen, Laura E.; Zepeda, Samantha K.; Bowen, John E.; Walls, Alexandra C.; Hauser, Kevin; Joshi, Anshu; Stewart, Cameron; Dillen, Josh R.; Powell, Abigail E.; Croll, Tristan I.; Nix, Jay; Virgin, Herbert W.; Corti, Davide; Snell, Gyorgy; Veesler, David

doi:10.1126/science.abn8652

Title: Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement

Journal Article · 24 January 2022 · Science

DOI: https://doi.org/10.1126/science.abn8652 · OSTI ID:1891296

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Univ. of Washington, Seattle, WA (United States)
Vir Biotechnology, San Francisco, CA (United States)
Univ. of Cambridge (United Kingdom)
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Vir Biotechnology, San Francisco, CA (United States); Washington Univ., St. Louis, MO (United States). School of Medicine; Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)
Humabs Biomed SA, Bellinzona, (Switzerland)

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.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC); National Institutes of Health (NIH); Burroughs Wellcome Fund; Fast Grants; University of Washington Arnold and Mabel Beckman Cryo-EM Center; National Institute of General Medical Sciences

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1891296

Journal Information:: Science, Journal Name: Science Journal Issue: 6583 Vol. 375; ISSN 0036-8075

Publisher:: AAASCopyright Statement

Country of Publication:: United States

Language:: English

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