A human monoclonal antibody neutralizes SARS-CoV-2 Omicron variants bytargeting the upstream region of spike protein HR2 motif  

作　　者：Hang Su Jun Zhang Zhenfei Yi Sajid Khan Mian Peng Liang Ye Alan Bao Han Zhang Guangli Suo Qian Li Housheng Zheng Dandan Wu Thomas J.Kipps Lanfeng Wang Zhenghong Lin Suping Zhang 

机构地区：[1]Shenzhen Key Laboratory of Precision Medicine for Hematological Malignancies,Guangdong Key Laboratory for Genome Stability andHuman Disease Prevention,Department of Pharmacology,School of Basic Medical Sciences,Base for International Science and TechnologyCooperation:Carson Cancer Stem Cell Vaccines R&D Center,International Cancer Center,Shenzhen University Medical School,ShenzhenUniversity,Guangdong,China [2]School of Life Sciences,Chongqing University,Chongqing,China [3]The Center for Microbes,Development and Health,CAS Key Laboratory of Molecular Virology&Immunology,Shanghai Institute of Immunityand Infection,Chinese Academy of Sciences,University of Chinese Academy of Sciences,Shanghai,China [4]College of Life Sciences,University of Chinese Academy of Sciences,Beijing,China [5]Department of Critical Care Medicine,Shenzhen Luohu People’s Hospital,Guangdong,China [6]University of California,Berkeley,California,USA [7]Xenta Biomedical Science Co.,Ltd,Guangdong,China [8]CAS Key Laboratory of Nano-Bio Interface,Suzhou Institute of Nano-Tech and Nano-Bionics,Chinese Academy of Sciences,Jiangsu,China [9]Center of Novel Therapeutics,University of California,San Diego,California,USA

出　　处：《hLife》2024年第3期126-140,共15页健康科学（英文）

基　　金：funded bythe National Natural Science Foundation of China(81972753,32170712,and 32170937);R&D Program of Guangzhou National Laboratory(SRPG22-003);the China Postdoctoral Science Foundation(2019M663093);Prevention and Control ofCOVID-2019 Research Program in University of GuangdongProvince(2020KZDZX1176);the Science and TechnologyProgram of Guangdong Province,China(2020A1515110410and 2021A1515010917);the Guangdong Medical Scienceand Technology Research Foundation(A2021336);ShenzhenKey Laboratory Foundation(ZDSYS20200811143757022);theShenzhen Science and Technology Basic Research Program(JCYJ20180507182203049 and JCYJ20230807142815034);and the Shenzhen University(SZU)Top Ranking Project(86000000210).

摘　　要：The continuous emergence of new severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants meansthere is a need to explore additional strategies to develop broad-spectrum vaccines or therapeutics for individuals remaining at risk of coronavirus disease 2019(COVID-19).Neutralizing monoclonal antibody(mAb)that binds to theconserved S2 subunit of the SARS-CoV-2 spike(S)protein alone,or in combination with mAb that binds to the receptor-binding domain(RBD)of S protein,might be effective in eliciting protection from infection by a variety of SARS-CoV2 variants.Using high-throughput single-cell immunoglobulin sequencing of B cells from COVID-19-convalescent donors,we identified a high-affinity S2-specific mAb-39,that could inhibit original SARS-CoV-2 strain,Omicron BA.1,BA.2.86,BA.4,BA.5,and EG.5.1 S protein-mediated membrane fusion,leading to the neutralization of these pseudoviralinfections.Moreover,mAb-39 could also improve the neutralizing activity of anti-RBD antibody against the highlyneutralization-resistant Omicron variants.Molecular docking and point mutation analyses revealed that mAb-39 recognized epitopes within the conserved upstream region of the heptad repeat 2(HR2)motif of the S2 subunit.Collectively,these findings demonstrate that targeting the conserved upstream region of the HR2 motif(e.g.,using mAbs)provides anovel strategy for preventing the infection of SARS-CoV-2 and its variants.

关 键 词：coronavirus disease 2019(COVID-19) severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron variants monoclonal antibody upstream region of heptad repeat 2(HR2) immunoglobulin repertoiresequencing 

分 类 号：R373[医药卫生—病原生物学]