1. Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement
- Author
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Matthew McCallum, Nadine Czudnochowski, Laura E. Rosen, Samantha K. Zepeda, John E. Bowen, Alexandra C. Walls, Kevin Hauser, Anshu Joshi, Cameron Stewart, Josh R. Dillen, Abigail E. Powell, Tristan I. Croll, Jay Nix, Herbert W. Virgin, Davide Corti, Gyorgy Snell, and David Veesler
- Subjects
Models, Molecular ,Protein Conformation ,General Science & Technology ,Antibodies, Viral ,Crystallography, X-Ray ,Article ,Antibodies ,Vaccine Related ,Protein Domains ,Models ,Biodefense ,Monoclonal ,Receptors ,Humans ,2.1 Biological and endogenous factors ,Protein Interaction Domains and Motifs ,Viral ,Aetiology ,Antigenic Drift and Shift ,Lung ,Immune Evasion ,Crystallography ,Multidisciplinary ,SARS-CoV-2 ,Prevention ,Cryoelectron Microscopy ,Antibodies, Monoclonal ,Molecular ,Pneumonia ,Spike Glycoprotein ,Coronavirus ,Emerging Infectious Diseases ,Infectious Diseases ,Amino Acid Substitution ,Spike Glycoprotein, Coronavirus ,Mutation ,X-Ray ,Pneumonia & Influenza ,Immunization ,Angiotensin-Converting Enzyme 2 ,Infection ,Broadly Neutralizing Antibodies ,Receptors, Coronavirus ,Protein Binding ,Biotechnology - Abstract
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.
- Published
- 2022