Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement.
- Resource Type
- Article
- Authors
- 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
- Source
- Science. 2/25/2022, Vol. 375 Issue 6583, p864-868. 5p. 5 Color Photographs.
- Subject
- *SARS-CoV-2 Omicron variant
*VACCINATION
*ANTIGENIC shift
*BINDING site assay
*X-ray crystallography
*GLYCOPROTEINS
- Language
- ISSN
- 0036-8075
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. [ABSTRACT FROM AUTHOR]