Structural Basis for the Enhanced Infectivity and Immune Evasion of Omicron Subvariants

Yaning Li; Yaping Shen; Yuanyuan Zhang; Renhong Yan

doi:10.3390/v15061398

Structural Basis for the Enhanced Infectivity and Immune Evasion of Omicron Subvariants

Viruses. 2023 Jun 20;15(6):1398. doi: 10.3390/v15061398.

Authors

Yaning Li^{1

2}, Yaping Shen¹, Yuanyuan Zhang¹, Renhong Yan³

Affiliations

¹ Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310024, China.
² Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
³ Key University Laboratory of Metabolism and Health of Guangdong, Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China.

Abstract

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.

Keywords: ACE2; Omicron subvariant; SARS-CoV-2; immune evasion; spike.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Humans
Immune Evasion
Pandemics
SARS-CoV-2 / genetics
Spike Glycoprotein, Coronavirus / genetics

Substances

Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2

Supplementary concepts

SARS-CoV-2 variants

Grants and funding

This research was funded by the Science, Technology and Innovation Commission of Shenzhen Municipality (JSGG20220226085550001 to R.Y.) and the start-up funds from the Southern University of Science and Technology (To R.Y.).