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



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.