An ultrapotent pan-β-coronavirus lineage B(β-CoV-B)neutralizing antibody locks the receptor-binding domain in closed conformation by targeting its conserved epitope

查看全文 作　　者：Zezhong [1]Liu;Wei [1]Xu;Zhenguo [1]Chen;Wangjun [2]Fu;Wuqiang [1]Zhan;Yidan [1]Gao;Jie [1]Zhou;Yunjiao [1]Zhou;Jianbo [1]Wu;Qian [1]Wang;Xiang [1]Zhang;Aihua [1]Hao;Wei [1]Wu;Qianqian [1]Zhang;Yaming [1]Li;Kaiyue [2]Fan;Ruihong [2]Chen;Qiaochu [1]Jiang;Christian [3]TMayer;Till [4]Schoofs;Youhua [1]Xie;Shibo [1]Jiang;Yumei [1]Wen;Zhenghong [1]Yuan;Kang [2]Wang;Lu [1]Lu;Lei [1]Sun;Qiao [1]Wang

机构地区：[1]Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS),School of Basic Medical Sciences,Shanghai Institute of Infectious Disease and Biosecurity,the Fifth People’s Hospital of Shanghai,Shanghai Key Laboratory of Medical Epigenetics,International Co-laboratory of Medical Epigenetics and Metabolism(Ministry of Science and Technology),Institutes of Biomedical Sciences,Biosafety Level 3 Laboratory,Shanghai Medical College,Fudan University,Shanghai 200032,China;[2]CAS Key Laboratory of Infection and Immunity,National Laboratory of Macromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China;[3]Experimental Immunology Branch,Center for Cancer Research,National Cancer Institute,National Institutes of Health,Bethesda,MD 20892,USA;[4]GSK Vaccines,1300 Wavre,Belgium

出　　处：《Protein & Cell》索引2022年第13卷第9期,共21页

基　　金：the National Natural Science Foundation of China(81822045 and 82041036 to L.L.,81900729 to L.S.,31872730 and 32070947 to Q.W.);the Program of Shanghai Academic/Technology Research Leader(20XD1420300 to L.L.). 摘　　要：New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design.Here,we identified a receptorbinding domain(RBD)-binding antibody,XG014,which potently neutralizesβ-coronavirus lineage B(β-CoV-B),including SARS-CoV-2,its circulating variants,SARSCoV and bat SARSr-CoV WIV1.Interestingly,antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibodydependent SARS-CoV-2 spike(S)protein-mediated cellcell fusion,suggesting a unique mode of recognition by XG014.Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional“down”conformation,while its family member XG005 directly competes with ACE2 binding and position the RBD“up”.Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo.Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines againstβ-CoV-B and newly emerging SARS-CoV-2 variants of concern. 关键词：SARS-CoV-2 neutralizing antibody receptor-binding domain XG014 antibody-dependent cellcell fusion

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An ultrapotent pan-β-coronavirus lineage B(β-CoV-B)neutralizing antibody locks the receptor-binding domain in closed conformation by targeting its conserved epitope

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