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TitleStructural Basis for the Enhanced Infectivity and Immune Evasion of Omicron Subvariants.
Journal, issue, pagesViruses, Vol. 15, Issue 6, Year 2023
Publish dateJun 20, 2023
AuthorsYaning Li / Yaping Shen / Yuanyuan Zhang / Renhong Yan /
PubMed AbstractThe Omicron variants of SARS-CoV-2 have emerged as the dominant strains worldwide, causing the COVID-19 pandemic. Each Omicron subvariant contains at least 30 mutations on the spike protein (S ...The Omicron variants of SARS-CoV-2 have emerged as the dominant strains worldwide, causing the COVID-19 pandemic. Each Omicron subvariant contains at least 30 mutations on the spike protein (S protein) compared to the original wild-type (WT) strain. Here we report the cryo-EM structures of the trimeric S proteins from the BA.1, BA.2, BA.3, and BA.4/BA.5 subvariants, with BA.4 and BA.5 sharing the same S protein mutations, each in complex with the surface receptor ACE2. All three receptor-binding domains of the S protein from BA.2 and BA.4/BA.5 are "up", while the BA.1 S protein has two "up" and one "down". The BA.3 S protein displays increased heterogeneity, with the majority in the all "up" RBD state. The different conformations preferences of the S protein are consistent with their varied transmissibility. By analyzing the position of the glycan modification on Asn343, which is located at the S309 epitopes, we have uncovered the underlying immune evasion mechanism of the Omicron subvariants. Our findings provide a molecular basis of high infectivity and immune evasion of Omicron subvariants, thereby offering insights into potential therapeutic interventions against SARS-CoV-2 variants.
External linksViruses / PubMed:37376697 / PubMed Central
MethodsEM (single particle)
Resolution2.8 - 4.1 Å
Structure data

EMDB-33575, PDB-7y1y:
S-ECD (Omicron BA.2) in complex with PD of ACE2
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-33576, PDB-7y1z:
S-ECD (Omicron BA.3) in complex with three PD of ACE2
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-33577, PDB-7y20:
S-ECD (Omicron BA.3) in complex with two PD of ACE2
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-33578, PDB-7y21:
S-ECD (Omicron BA.5) in complex with PD of ACE2
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-33579: map focused on the interface between BA.2 RBD and ACE2
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-33580: map focused on the interface between BA.3 RBD and ACE2
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-33581: map focused on the interface between BA.4 RBD and ACE2
Method: EM (single particle) / Resolution: 3.1 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/HYDROLASE / SARS-Cov-2 / VIRAL PROTEIN / VIRAL PROTEIN-HYDROLASE complex

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