Cryo-EM structures of SARS-CoV-2 Omicron BA.2 spike

Cell Rep. 2022 Jun 28;39(13):111009. doi: 10.1016/j.celrep.2022.111009. Epub 2022 Jun 8.

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 sub-lineage has gained in proportion relative to BA.1. Because spike (S) protein variations may underlie differences in their pathobiology, here we determine cryoelectron microscopy (cryo-EM) structures of the BA.2 S ectodomain and compare these with previously determined BA.1 S structures. BA.2 receptor-binding domain (RBD) mutations induce remodeling of the RBD structure, resulting in tighter packing and improved thermostability. Interprotomer RBD interactions are enhanced in the closed (or 3-RBD-down) BA.2 S, while the fusion peptide is less accessible to antibodies than in BA.1. Binding and pseudovirus neutralization assays reveal extensive immune evasion while defining epitopes of two outer RBD face-binding antibodies, DH1044 and DH1193, that neutralize both BA.1 and BA.2. Taken together, our results indicate that stabilization of the closed state through interprotomer RBD-RBD packing is a hallmark of the Omicron variant and show differences in key functional regions in the BA.1 and BA.2 S proteins.

Keywords: CP: Microbiology; Omicron BA.2; SARS-CoV-2 spike; cryoelectron microscopy; fusion peptide; immune evasion; receptor binding domain.

MeSH terms

  • Antibodies, Viral
  • COVID-19*
  • Cryoelectron Microscopy
  • Humans
  • Receptors, Virus / metabolism
  • SARS-CoV-2*
  • Spike Glycoprotein, Coronavirus

Substances

  • Antibodies, Viral
  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Supplementary concepts

  • SARS-CoV-2 variants