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Ling Zhu Yong-Qiang Deng Rong-Rong Zhang Zhen Cui Chun-Yun Sun Chang-Fa Fan Xiaorui Xing Weijin Huang Qi Chen Na-Na Zhang Qing Ye Tian-Shu Cao Nan Wang Lei Wang Lei Cao Huiyu Wang Desheng Kong Juan Ma Chunxia Luo Yanjing Zhang Jianhui Nie Yao Sun Zhe Lv Neil Shaw Qianqian Li Xiao-Feng Li Junjie Hu Liangzhi Xie Zihe Rao Youchun Wang Xiangxi Wang Cheng-Feng Qin 《国家科学评论(英文版)》2021,8(3):24-36
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. 相似文献
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