SARS-CoV-2 Omicron Variant: ACE2 Binding, Cryo-EM Structure of Spike Protein-ACE2 Complex and Antibody Evasion
SARS-CoV-2 Omicron Variant: ACE2 Binding, Cryo-EM Structure of Spike Protein-ACE2 Complex and Antibody Evasion
The newly reported Omicron variant is poised to replace Delta as the most rapidly spread SARS-CoV-2 variant across the world. Cryo-EM structural analysis of the Omicron variant spike protein in complex with human ACE2 reveals new salt bridges and hydrogen bonds formed by mutated residues R493, S496 and R498 in the RBD with ACE2. These interactions appear to compensate for other Omicron mutations such as K417N known to reduce ACE2 binding affinity, explaining our finding of similar biochemical ACE2 binding affinities for Delta and Omicron variants. Neutralization assays show that pseudoviruses displaying the Omicron spike protein exhibit increased antibody evasion, with greater evasion observed in sera obtained from unvaccinated convalescent patients as compared to doubly vaccinated individuals (8-vs 3-fold). The retention of strong interactions at the ACE2 interface and the increase in antibody evasion are molecular factors that likely contribute to the increased transmissibility of the Omicron variant.
Zhu Xing、Srivastava Shanti S.、Berezuk Alison M.、Sekirov Inna、Mannar Dhiraj、Marquez Citlali、Tuttle Katharine S.、Saville James W.、Subramaniam Sriram
Department of Biochemistry and Molecular Biology, University of British ColumbiaDepartment of Biochemistry and Molecular Biology, University of British ColumbiaDepartment of Biochemistry and Molecular Biology, University of British ColumbiaBC Center for Disease Control Public Health Laboratory||Department of Pathology and Laboratory Medicine, University of British ColumbiaDepartment of Biochemistry and Molecular Biology, University of British ColumbiaBC Center for Disease Control Public Health LaboratoryDepartment of Biochemistry and Molecular Biology, University of British ColumbiaDepartment of Biochemistry and Molecular Biology, University of British ColumbiaDepartment of Biochemistry and Molecular Biology, University of British Columbia||Gandeeva Therapeutics Inc.
基础医学生物科学研究方法、生物科学研究技术分子生物学
Zhu Xing,Srivastava Shanti S.,Berezuk Alison M.,Sekirov Inna,Mannar Dhiraj,Marquez Citlali,Tuttle Katharine S.,Saville James W.,Subramaniam Sriram.SARS-CoV-2 Omicron Variant: ACE2 Binding, Cryo-EM Structure of Spike Protein-ACE2 Complex and Antibody Evasion[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2021.12.19.473380.点此复制
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