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…

• UD
  U.S. Department of Energy

  Awards: -AC02-05CH11231, 05CH11231, AC02-05CH11231, DE-AC02, DE-AC02-05CH11231, DE-AC02-
• UO
  University of Washington
• WT
  Wellcome Trust

  Awards: Z/17/Z, 209407/Z/17/Z
• FG
  Fast Grants
• NI
  National Institutes of Health

  Awards: S10OD032290, DE-AC02-05CH11231, HHSN272201700059C
• OO
  Office of Science

  Awards: AC02-05CH11231, -AC02-05CH11231, DE-AC02
• NI
  National Institute of Allergy and Infectious Diseases

  Awards: HHSN272201700059C, DP1AI158186