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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Stalls, V; Lindenberger, J; Gobeil, SM-C; Henderson, R; Parks, R; Barr, M; Deyton, M; Martin, M; Janowska, K; Huang, X; May, A; Speakman, M; Beaudoin, E; Kraft, B; Lu, X; Edwards, RJ; Eaton, A; Montefiori, DC; Williams, WB; Saunders, KO; Wiehe, K; Haynes, BF; Acharya, P

Published Date

  • June 28, 2022

Published In

Volume / Issue

  • 39 / 13

Start / End Page

  • 111009 -

PubMed ID

  • 35732171

Pubmed Central ID

  • PMC9174147

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2022.111009


  • eng

Conference Location

  • United States