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

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

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Intensive selection pressure constrains the evolutionary trajectory of SARS-CoV-2 genomes and results in vari-ous 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 main-tained,emphasizing the significance of comprehensive assessment of spike mutations.

SARS-CoV-2RBD mutationantibody evasionACE2 affinityvariant of concernviral evolution

Song Xue、Yuru Han、Fan Wu、Qiao Wang

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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

National Key Research and Development ProgramNational Key Research and Development ProgramNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaShanghai Municipal Science and Technology Major ProjectNonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences

2023YFC08726002021YFA13014003207094732370943ZD2021CY0012023-PT310-02

2024

10.1093/procel/pwae007

蛋白质与细胞

蛋白质与细胞

CSTPCD
影响因子：0.645
ISSN：
年,卷(期)：2024.15(6)