A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes
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Published:2021-05-11
Issue:1
Volume:12
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Guo YuORCID, Huang Lisu, Zhang Guangshun, Yao Yanfeng, Zhou He, Shen ShuORCID, Shen Bingqing, Li Bo, Li Xin, Zhang Qian, Chen Mingjie, Chen Da, Wu Jia, Fu Dan, Zeng Xinxin, Feng Mingfang, Pi Chunjiang, Wang Yuan, Zhou XingdongORCID, Lu Minmin, Li Yarong, Fang Yaohui, Lu Yun-Yueh, Hu Xue, Wang Shanshan, Zhang Wanju, Gao Ge, Adrian Francisco, Wang QishengORCID, Yu Feng, Peng Yun, Gabibov Alexander G., Min Juan, Wang Yuhui, Huang Heyu, Stepanov AlexeyORCID, Zhang WeiORCID, Cai Yan, Liu Junwei, Yuan ZhimingORCID, Zhang Chen, Lou ZhiyongORCID, Deng FeiORCID, Zhang HongkaiORCID, Shan ChaoORCID, Schweizer LiangORCID, Sun KunORCID, Rao ZiheORCID
Abstract
AbstractCOVID-19 pandemic caused by SARS-CoV-2 constitutes a global public health crisis with enormous economic consequences. Monoclonal antibodies against SARS-CoV-2 can provide an important treatment option to fight COVID-19, especially for the most vulnerable populations. In this work, potent antibodies binding to SARS-CoV-2 Spike protein were identified from COVID-19 convalescent patients. Among them, P4A1 interacts directly with and covers majority of the Receptor Binding Motif of the Spike Receptor-Binding Domain, shown by high-resolution complex structure analysis. We further demonstrate the binding and neutralizing activities of P4A1 against wild type and mutant Spike proteins or pseudoviruses. P4A1 was subsequently engineered to reduce the potential risk for Antibody-Dependent Enhancement of infection and to extend its half-life. The engineered antibody exhibits an optimized pharmacokinetic and safety profile, and it results in complete viral clearance in a rhesus monkey model of COVID-19 following a single injection. These data suggest its potential against SARS-CoV-2 related diseases.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
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