Mutations in the SARS-CoV-2 spike receptor binding domain and their delicate balance between ACE2 affinity and antibody evasion  

作　　者：Song Xue Yuru Han Fan Wu Qiao Wang 

机构地区：[1]Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS),Shanghai Institute of Infectious Disease and Biosecurity,Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection,School of Basic Medical Sciences,Shanghai Medical College,Fudan University,Shanghai 200032,China

出　　处：《Protein & Cell》2024年第6期403-418,共16页蛋白质与细胞（英文版）

基　　金：supported by the National Key Research and Development Program(2023YFC0872600 and 2021YFA1301400);the National Natural Science Foundation of China(32070947 and 32370943);the Shanghai Municipal Science and Technology Major Project(ZD2021CY001);supported by the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2023-PT310-02).

摘　　要：Intensive selection pressure constrains the evolutionary trajectory of SARS-CoV-2 genomes and results in various novel variants with distinct mutation profiles.Point mutations,particularly those within the receptor binding domain(RBD)of SARS-CoV-2 spike(S)protein,lead to the functional alteration in both receptor engagement and monoclonal antibody(mAb)recognition.Here,we review the data of the RBD point mutations possessed by major SARS-CoV-2 variants and discuss their individual effects on ACE2 affinity and immune evasion.Many single amino acid substitutions within RBD epitopes crucial for the antibody evasion capacity may conversely weaken ACE2 binding affinity.However,this weakened effect could be largely compensated by specific epistatic mutations,such as N501Y,thus maintaining the overall ACE2 affinity for the spike protein of all major variants.The predominant direction of SARS-CoV-2 evolution lies neither in promoting ACE2 affinity nor evading mAb neutralization but in maintaining a delicate balance between these two dimensions.Together,this review interprets how RBD mutations efficiently resist antibody neutralization and meanwhile how the affinity between ACE2 and spike protein is maintained,emphasizing the significance of comprehensive assessment of spike mutations.

关 键 词：ACE2 AFFINITY maintained 

分 类 号：Q939.4[生物学—微生物学]