Double lock of a potent human therapeutic monoclonal antibody against SARS-CoV-2     

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)

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