Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement.
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.
Mesh Terms:
Amino Acid Substitution, Angiotensin-Converting Enzyme 2, Antibodies, Monoclonal, Antibodies, Viral, Antigenic Drift and Shift, Broadly Neutralizing Antibodies, Cryoelectron Microscopy, Crystallography, X-Ray, Humans, Immune Evasion, Models, Molecular, Mutation, Protein Binding, Protein Conformation, Protein Domains, Protein Interaction Domains and Motifs, Receptors, Coronavirus, SARS-CoV-2, Spike Glycoprotein, Coronavirus
Amino Acid Substitution, Angiotensin-Converting Enzyme 2, Antibodies, Monoclonal, Antibodies, Viral, Antigenic Drift and Shift, Broadly Neutralizing Antibodies, Cryoelectron Microscopy, Crystallography, X-Ray, Humans, Immune Evasion, Models, Molecular, Mutation, Protein Binding, Protein Conformation, Protein Domains, Protein Interaction Domains and Motifs, Receptors, Coronavirus, SARS-CoV-2, Spike Glycoprotein, Coronavirus
Science
Date: Dec. 25, 2021
PubMed ID: 35076256
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