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Neutralization mechanism of a human antibody with pan-coronavirus reactivity including SARS-CoV-2.
Sun, Xiaoyu; Yi, Chunyan; Zhu, Yuanfei; Ding, Longfei; Xia, Shuai; Chen, Xingchen; Liu, Mu; Gu, Chenjian; Lu, Xiao; Fu, Yadong; Chen, Shuangfeng; Zhang, Tianlong; Zhang, Yaguang; Yang, Zhuo; Ma, Liyan; Gu, Wangpeng; Hu, Gaowei; Du, Shujuan; Yan, Renhong; Fu, Weihui; Yuan, Songhua; Qiu, Chenli; Zhao, Chen; Zhang, Xiaoyan; He, Yonghui; Qu, Aidong; Zhou, Xu; Li, Xiuling; Wong, Gary; Deng, Qiang; Zhou, Qiang; Lu, Hongzhou; Ling, Zhiyang; Ding, Jianping; Lu, Lu; Xu, Jianqing; Xie, Youhua; Sun, Bing.
  • Sun X; State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • Yi C; State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • Zhu Y; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai Medical College, Fudan University, Shanghai, China.
  • Ding L; Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
  • Xia S; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai Medical College, Fudan University, Shanghai, China.
  • Chen X; State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • Liu M; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai Medical College, Fudan University, Shanghai, China.
  • Gu C; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai Medical College, Fudan University, Shanghai, China.
  • Lu X; State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • Fu Y; State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • Chen S; State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • Zhang T; School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • Zhang Y; Institute of Geriatrics, Affiliated Nantong Hospital of Shanghai University, Sixth People's Hospital of Nantong, Shanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, Nantong, China.
  • Yang Z; State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • Ma L; State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • Gu W; State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • Hu G; State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • Du S; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai Medical College, Fudan University, Shanghai, China.
  • Yan R; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai Medical College, Fudan University, Shanghai, China.
  • Fu W; Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China.
  • Yuan S; Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
  • Qiu C; Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
  • Zhao C; Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
  • Zhang X; Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
  • He Y; Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
  • Qu A; State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • Zhou X; Shanghai Institute of Biological Products Co., Ltd, Shanghai, China.
  • Li X; Shanghai Institute of Biological Products Co., Ltd, Shanghai, China.
  • Wong G; Shanghai Institute of Biological Products Co., Ltd, Shanghai, China.
  • Deng Q; Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
  • Zhou Q; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai Medical College, Fudan University, Shanghai, China.
  • Lu H; Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China.
  • Ling Z; Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
  • Ding J; State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China. lingzhiyang@sibs.ac.cn.
  • Lu L; State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China. jpding@sibcb.ac.cn.
  • Xu J; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai Medical College, Fudan University, Shanghai, China. lul@fudan.edu.cn.
  • Xie Y; Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China. lul@fudan.edu.cn.
  • Sun B; Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China. xujianqing@fudan.edu.cn.
Nat Microbiol ; 7(7): 1063-1074, 2022 07.
Article in English | MEDLINE | ID: covidwho-1908191
ABSTRACT
Frequent outbreaks of coronaviruses underscore the need for antivirals and vaccines that can counter a broad range of coronavirus types. We isolated a human antibody named 76E1 from a COVID-19 convalescent patient, and report that it has broad-range neutralizing activity against multiple α- and ß-coronaviruses, including the SARS-CoV-2 variants. 76E1 also binds its epitope in peptides from γ- and δ-coronaviruses. 76E1 cross-protects against SARS-CoV-2 and HCoV-OC43 infection in both prophylactic and therapeutic murine animal models. Structural and functional studies revealed that 76E1 targets a unique epitope within the spike protein that comprises the highly conserved S2' site and the fusion peptide. The epitope that 76E1 binds is partially buried in the structure of the SARS-CoV-2 spike trimer in the prefusion state, but is exposed when the spike protein binds to ACE2. This observation suggests that 76E1 binds to the epitope at an intermediate state of the spike trimer during the transition from the prefusion to the postfusion state, thereby blocking membrane fusion and viral entry. We hope that the identification of this crucial epitope, which can be recognized by 76E1, will guide epitope-based design of next-generation pan-coronavirus vaccines and antivirals.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Observational study / Prognostic study / Randomized controlled trials Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: Nat Microbiol Year: 2022 Document Type: Article Affiliation country: S41564-022-01155-3

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Observational study / Prognostic study / Randomized controlled trials Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: Nat Microbiol Year: 2022 Document Type: Article Affiliation country: S41564-022-01155-3