2021/12/31 by Matthew McCallum, Nadine Czudnochowski, Laura E. Rosen +10 · 1 citation
Medicine · Biochemistry, Genetics and Molecular Biology · #SARS-CoV-2 and COVID-19 Research #Bacillus and Francisella bacterial research #Virus-based gene therapy research
paper · pdf · doi:10.1101/2021.12.28.474380
openalex publication_date 2021/12/31 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
The SARS-CoV-2 Omicron variant of concern evades antibody mediated immunity with an unprecedented magnitude 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 and RBD bound to the broadly neutralizing sarbecovirus monoclonal antibody (mAb) S309 (the parent mAb of sotrovimab) and to the human ACE2 receptor. We provide a structural framework for understanding the marked reduction of binding of all other therapeutic mAbs leading to dampened neutralizing activity. We reveal electrostatic remodeling of the interactions within the spike and those formed between the Omicron RBD and human ACE2, likely explaining enhanced affinity for the host receptor relative to the prototypic virus.