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.
【저자키워드】 immune evasion, Cryoelectron microscopy, fusion peptide, Omicron BA.2, CP: Microbiology, receptor binding domain., SARS-CoV-2 spike, 【초록키워드】 Structure, antibodies, SARS-CoV-2, coronavirus, Mutation, Microbiology, antibody, Variation, variant, peptide, severe acute respiratory syndrome Coronavirus, omicron, immune, Receptor binding domain, Protein, immune evasion, Epitopes, Region, RBD, Microscopy, Lineage, Omicron variant, cryo-EM, Cryoelectron microscopy, respiratory, binding antibodies, fusion peptide, epitope, Pseudovirus neutralization assay, SARS-CoV-2 spike, Interaction, structures, acute respiratory syndrome, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, domain, S proteins, ectodomain, hallmark, remodeling, neutralize, resulting, proportion, functional, less, determine, the RBD, induce, underlie, 【제목키워드】 Structure, SARS-CoV-2,