A systematic mutation analysis of 13 major SARS-CoV-2 variants

Han Bai; Xuan Zhang; Tian Gong; Junpeng Ma; Peng Zhang; Zeqiong Cai; Doudou Ren; Chengsheng Zhang

doi:10.1016/j.virusres.2024.199392

A systematic mutation analysis of 13 major SARS-CoV-2 variants

Virus Res. 2024 May 14:345:199392. doi: 10.1016/j.virusres.2024.199392. Online ahead of print.

Authors

Han Bai¹, Xuan Zhang², Tian Gong², Junpeng Ma², Peng Zhang², Zeqiong Cai¹, Doudou Ren¹, Chengsheng Zhang³

Affiliations

¹ The MED-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Building 21, Western China Science and Technology Innovation Harbor, Xi'an 710000, China.
² Center for Molecular Diagnosis and Precision Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 1519 Dongyue Dadao, Nanchang 330209, China; Department of Clinical Laboratory, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 17 Yongwai Zhengjie, Nanchang 330006, China; Jiangxi Provincial Center for Advanced Diagnostic Technology and Precision Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 1519 Dongyue Dadao, Nanchang 330209, China; Department of Medical Genetics, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 1519 DongYue Dadao, Nanchang 330209, China.
³ The MED-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Building 21, Western China Science and Technology Innovation Harbor, Xi'an 710000, China; Center for Molecular Diagnosis and Precision Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 1519 Dongyue Dadao, Nanchang 330209, China; Department of Clinical Laboratory, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 17 Yongwai Zhengjie, Nanchang 330006, China; Jiangxi Provincial Center for Advanced Diagnostic Technology and Precision Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 1519 Dongyue Dadao, Nanchang 330209, China; Department of Medical Genetics, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 1519 DongYue Dadao, Nanchang 330209, China. Electronic address: ndyfy09564@ncu.edu.cn.

Abstract

SARS-CoV-2 evolves constantly with various novel mutations. Due to their enhanced infectivity, transmissibility and immune evasion, a comprehensive understanding of the association between these mutations and the respective functional changes is crucial. However, previous mutation studies of major SARS-CoV-2 variants remain limited. Here, we performed systematic analyses of full-length amino acids mutation, phylogenetic features, protein physicochemical properties, molecular dynamics and immune escape as well as pseudotype virus infection assays among thirteen major SARS-CoV-2 variants. We found that Omicron exhibited the most abundant and complex mutation sites, higher indices of hydrophobicity and flexibility than other variants. The results of molecular dynamics simulation suggest that Omicron has the highest number of hydrogen bonds and strongest binding free energy between the S protein and ACE2 receptor. Furthermore, we revealed 10 immune escape sites in 13 major variants, some of them were reported previously, but four of which (i.e. 339/373/477/496) are first reported to be specific to Omicron, whereas 462 is specific to Epslion. The infectivity of these variants was confirmed by the pseudotype virus infection assays. Our findings may help us understand the functional consequences of the mutations within various variants and the underlying mechanisms of the immune escapes conferred by the S proteins.

Keywords: Molecular dynamics analysis; Mutation; SARS-CoV-2; Sequence analysis; Spike protein; Variants.