Double Lock of a Potent Human Monoclonal Antibody against SARS-CoV-2
Author:
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 XiangxiORCID, Qin Cheng-Feng
Abstract
SummaryReceptor 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-fold of 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 ACE2 receptor. Binding of the antibody also restrains any further conformational changes of the RBD, 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.HighlightsSARS-CoV-2 specific antibody, HB27, blocks viral receptor binding and membrane fusionHB27 confers prophylactic and therapeutic protection against SARS-CoV-2 in mice modelsRhesus macaques showed no adverse side effects when administered with HB27Cryo-EM studies suggest that HB27 sterically occludes SARS-CoV-2 from its receptor
Publisher
Cold Spring Harbor Laboratory
Reference45 articles.
1. Towards automated crystallographic structure refinement with phenix.refine 2. Brouwer, P.J.M. , Caniels, T.G. , van der Straten, K. , Snitselaar, J.L. , Aldon, Y. , Bangaru, S. , Torres, J.L. , Okba, N.M.A. , Claireaux, M. , Kerster, G. , et al. (2020). Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. Science. 3. Tools for macromolecular model building and refinement into electron cryo-microscopy reconstructions;Acta Crystallographica Section D-Structural Biology,2015 4. Cao, Y. , Su, B. , Guo, X. , Sun, W. , Deng, Y. , Bao, L. , Zhu, Q. , Zhang, X. , Zheng, Y. , Geng, C. , et al. (2020). Potent neutralizing antibodies against SARS-CoV-2 identified by high-throughput single-cell sequencing of convalescent patients’ B cells. Cell. 5. MolProbity: all-atom structure validation for macromolecular crystallography
Cited by
4 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献
|
|