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Double lock of a potent human therapeutic monoclonal antibody against SARS-CoV-2.
Zhu, Ling; Deng, Yong-Qiang; Zhang, Rong-Rong; Cui, Zhen; Sun, Chun-Yun; Fan, Chang-Fa; Xing, Xiaorui; Huang, Weijin; Chen, Qi; Zhang, Na-Na; Ye, Qing; Cao, Tian-Shu; Wang, Nan; Wang, Lei; Cao, Lei; Wang, Huiyu; Kong, Desheng; Ma, Juan; Luo, Chunxia; Zhang, Yanjing; Nie, Jianhui; Sun, Yao; Lv, Zhe; Shaw, Neil; Li, Qianqian; Li, Xiao-Feng; Hu, Junjie; Xie, Liangzhi; Rao, Zihe; Wang, Youchun; Wang, Xiangxi; Qin, Cheng-Feng.
  • Zhu L; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • Deng YQ; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, China.
  • Zhang RR; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, China.
  • Cui Z; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • Sun CY; Beijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing 100176, China.
  • Fan CF; Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China.
  • Xing X; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • Huang W; Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, NIFDC, Beijing 102629, China.
  • Chen Q; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, China.
  • Zhang NN; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, China.
  • Ye Q; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, China.
  • Cao TS; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, China.
  • Wang N; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • Wang L; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • Cao L; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • Wang H; Beijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing 100176, China.
  • Kong D; Beijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing 100176, China.
  • Ma J; Beijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing 100176, China.
  • Luo C; Beijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing 100176, China.
  • Zhang Y; Beijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing 100176, China.
  • Nie J; Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, NIFDC, Beijing 102629, China.
  • Sun Y; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • Lv Z; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • Shaw N; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • Li Q; Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, NIFDC, Beijing 102629, China.
  • Li XF; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, China.
  • Hu J; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • Xie L; Beijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing 100176, China.
  • Rao Z; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • Wang Y; Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, NIFDC, Beijing 102629, China.
  • Wang X; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • Qin CF; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, China.
Natl Sci Rev ; 8(3): nwaa297, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-990776
ABSTRACT
Receptor recognition and subsequent membrane fusion are essential for the establishment of successful infection by SARS-CoV-2. Halting these steps can cure COVID-19. Here we have identified and characterized a potent human monoclonal antibody, HB27, that blocks SARS-CoV-2 attachment to its cellular receptor at sub-nM concentrations. Remarkably, HB27 can also prevent SARS-CoV-2 membrane fusion. Consequently, a single dose of HB27 conferred effective protection against SARS-CoV-2 in two established mouse models. Rhesus macaques showed no obvious adverse events when administrated with 10 times the effective dose of HB27. Cryo-EM studies on complex of SARS-CoV-2 trimeric S with HB27 Fab reveal that three Fab fragments work synergistically to occlude SARS-CoV-2 from binding to the ACE2 receptor. Binding of the antibody also restrains any further conformational changes of the receptor binding domain, possibly interfering with progression from the prefusion to the postfusion stage. These results suggest that HB27 is a promising candidate for immuno-therapies against COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Topics: Vaccines Language: English Journal: Natl Sci Rev Year: 2021 Document Type: Article Affiliation country: Nsr

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Full text: Available Collection: International databases Database: MEDLINE Topics: Vaccines Language: English Journal: Natl Sci Rev Year: 2021 Document Type: Article Affiliation country: Nsr