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 Song Xue;Yuru Han;Fan Wu;Qiao Wang

作者机构：Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS)Shanghai Institute of Infectious Disease and BiosecurityShanghai Frontiers Science Center of Pathogenic Microorganisms and InfectionSchool of Basic Medical SciencesShanghai Medical CollegeFudan UniversityShanghai 200032China 

出 版 物：《Protein & Cell》 (蛋白质与细胞（英文版）)

年 卷 期：2024年第15卷第6期

页      面：403-418页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 07[理学] 071005[理学-微生物学] 10[医学] 

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) 

主　　题：ACE2 affinity maintained 

摘      要：Intensive selection pressure constrains the evolutionary trajectory of SARS-CoV-2 genomes and results in various novel variants with distinct mutation *** 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)***,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 *** single amino acid substitutions within RBD epitopes crucial for the antibody evasion capacity may conversely weaken ACE2 binding ***,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 *** 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 ***,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.