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  

作　　者：Zezhong Liu Wei Xu Zhenguo Chen Wangjun Fu Wuqiang Zhan Yidan Gao Jie Zhou Yunjiao Zhou Jianbo Wu Qian Wang Xiang Zhang Aihua Hao Wei Wu Qianqian Zhang Yaming Li Kaiyue Fan Ruihong Chen Qiaochu Jiang Christian TMayer Till Schoofs Youhua Xie Shibo Jiang Yumei Wen Zhenghong Yuan Kang Wang Lu Lu Lei Sun Qiao 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》2022年第9期655-675,共21页蛋白质与细胞（英文版）

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 

分 类 号：R56[医药卫生—呼吸系统]