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

[tetano]

Cell Rep


. 2022 Jun 8;111009.
doi: 10.1016/j.celrep.2022.111009. Online ahead of print.
Cryo-EM structures of SARS-CoV-2 Omicron BA.2 spike


Victoria Stalls ¹ , Jared Lindenberger ¹ , Sophie M-C Gobeil ¹ , Rory Henderson ² , Rob Parks ¹ , Maggie Barr ¹ , Margaret Deyton ¹ , Mitchell Martin ¹ , Katarzyna Janowska ¹ , Xiao Huang ¹ , Aaron May ³ , Micah Speakman ¹ , Esther Beaudoin ¹ , Bryan Kraft ⁴ , Xiaozhi Lu ¹ , Robert J Edwards ² , Amanda Eaton ¹ , David C Montefiori ⁵ , Wilton B Williams ³ , Kevin O Saunders ⁵ , Kevin Wiehe ² , Barton F Haynes ⁶ , Priyamvada Acharya ⁷



Affiliations

• PMID: 35732171
• DOI: 10.1016/j.celrep.2022.111009

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.