EMD-34038

Single-particle
3.72 Å
EMD-34038 Deposition: 08/08/2022
Map released: 19/10/2022
Last modified: 06/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-34038

SARS-CoV-2 BA.2.75 S Trimer in complex with S309 (state1)

EMD-34038

Single-particle
3.72 Å
EMD-34038 Deposition: 08/08/2022
Map released: 19/10/2022
Last modified: 06/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens, Severe acute respiratory syndrome coronavirus 2
Sample: BA.2.75 S trimer in complex with S309
Fitted models: 7yqx (Avg. Q-score: 0.353)

Deposition Authors: Wang L
Characterization of the enhanced infectivity and antibody evasion of Omicron BA.2.75.
PUBMED: 36270286
DOI: doi:10.1016/j.chom.2022.09.018
ISSN: 1934-6069
Abstract:
Recently emerged SARS-CoV-2 Omicron subvariant, BA.2.75, displayed a growth advantage over circulating BA.2.38, BA.2.76, and BA.5 in India. However, the underlying mechanisms for enhanced infectivity, especially compared with BA.5, remain unclear. Here, we show that BA.2.75 exhibits substantially higher affinity for host receptor angiotensin-converting enzyme 2 (ACE2) than BA.5 and other variants. Structural analyses of BA.2.75 spike shows its decreased thermostability and increased frequency of the receptor binding domain (RBD) in the "up" conformation under acidic conditions, suggesting enhanced low-pH-endosomal cell entry. Relative to BA.4/BA.5, BA.2.75 exhibits reduced evasion of humoral immunity from BA.1/BA.2 breakthrough-infection convalescent plasma but greater evasion of Delta breakthrough-infection convalescent plasma. BA.5 breakthrough-infection plasma also exhibits weaker neutralization against BA.2.75 than BA.5, mainly due to BA.2.75's distinct neutralizing antibody (NAb) escape pattern. Antibody therapeutics Evusheld and Bebtelovimab remain effective against BA.2.75. These results suggest BA.2.75 may prevail after BA.4/BA.5, and its increased receptor-binding capability could support further immune-evasive mutations.