Altered hACE2 binding affinity and S1/S2 cleavage efficiency of SARS-CoV-2 spike protein mutants affect viral cell entry
作者机构：National Key Laboratory of BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing100101China Faculty of Synthetic BiologyShenzhen Institute of Advanced TechnologyShenzhen518055China University of Chinese Academy of SciencesBeijing100101China
出 版 物：《Virologica Sinica》 (中国病毒学（英文版）)
年 卷 期：2023年第38卷第4期
页 面：595-605页
核心收录：
学科分类：1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 1001[医学-基础医学(可授医学、理学学位)] 100103[医学-病原生物学] 10[医学]
基 金：supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No.XDB29050100) the National Key Research and Development Program of China (Grant No.2022YFC0869900,2022YFC2303501,2020YFC0861100) the Program of the Chinese Academy of Sciences (Grant No.2020YJFK-Z-0150)
主 题：SARS-CoV-2 Variants of Concern(VOC) Omicron Binding affinity Viral entry Host-tropism
摘 要：SARS-CoV-2 variants are constantly emerging,hampering public health measures in controlling the number of *** it is well established that mutations in spike proteins observed for the different variants directly affect virus entry into host cells,there remains a need for further expansion of systematic and multifaceted ***,we comprehensively studied the effect of spike protein mutations on spike expression and proteolytic activation,binding affinity,viral entry efficiency and host cell tropism of eight variants of concern(VOC)and variants of interest(VOI).We found that both the full-length spike and its receptor-binding domain(RBD)of Omicron bind to hACE2 with an affinity similar to that of the *** addition,Alpha,Beta,Delta and Lambda pseudoviruses gained significantly enhanced cell entry ability compared to the wild-type,while the Omicron pseudoviruses showed a slightly increased cell entry,suggesting the vastly increased rate of transmission observed for Omicron variant is not associated with its affinity to *** also found that the spikes of Omicron and Mu showed lower S1/S2 cleavage efficiency and inefficiently utilized TMPRSS2 to enter host cells than others,suggesting that they prefer the endocytosis pathway to enter host ***,all variants pseudoviruses we tested gained the ability to enter the animal ACE2-expressing *** the infection potential of rats and mice showed significantly increased,strongly suggesting that rodents possibly become a reservoir for viral *** insights gained from this study provide valuable guidance for a targeted approach to epidemic control,and contribute to a better understanding of SARS-CoV-2 evolution.
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