
Cryo-EM structures of SARS-CoV-2 Omicron BA.2 spike.
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.
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- Spike Glycoprotein, Coronavirus
- SARS-CoV-2
- Receptors, Virus
- Humans
- Cryoelectron Microscopy
- COVID-19
- Antibodies, Viral
- 31 Biological sciences
- 1116 Medical Physiology
- 0601 Biochemistry and Cell Biology
Citation

Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Spike Glycoprotein, Coronavirus
- SARS-CoV-2
- Receptors, Virus
- Humans
- Cryoelectron Microscopy
- COVID-19
- Antibodies, Viral
- 31 Biological sciences
- 1116 Medical Physiology
- 0601 Biochemistry and Cell Biology