1. A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes
- Author
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Dan Fu, Mingjie Chen, Yuhui Wang, Wei Zhang, Zihe Rao, Zhiming Yuan, Chen Zhang, Zhiyong Lou, Lisu Huang, W.J. Zhang, Chunjiang Pi, Shu Shen, Mingfang Feng, Yuan Wang, Xue Hu, Hongkai Zhang, Da Chen, Ge Gao, Minmin Lu, Feng Yu, Yun-Yueh Lu, Yu Guo, Francisco Adrian, Bingqing Shen, Yanfeng Yao, Liang Schweizer, Alexey Stepanov, Yarong Li, Junwei Liu, Qisheng Wang, Fei Deng, Xin Li, Jia Wu, Bo Li, Juan Min, He Zhou, Shanshan Wang, Kun Sun, Qian Zhang, Heyu Huang, X.Q. Zeng, Alexander G. Gabibov, Yun Peng, Xingdong Zhou, Chao Shan, Yan Cai, Yaohui Fang, and Guangshun Zhang
- Subjects
Male ,0301 basic medicine ,medicine.drug_class ,Science ,Protein domain ,Mutant ,General Physics and Astronomy ,Plasma protein binding ,Biology ,Antibodies, Viral ,Monoclonal antibody ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,Protein Domains ,Antibody Specificity ,Cell Line, Tumor ,Chlorocebus aethiops ,medicine ,Animals ,Humans ,Neutralizing antibody ,skin and connective tissue diseases ,Pandemics ,Vero Cells ,Cells, Cultured ,Multidisciplinary ,SARS-CoV-2 ,fungi ,Wild type ,Antibodies, Monoclonal ,COVID-19 ,General Chemistry ,Antibodies, Neutralizing ,Macaca mulatta ,Virology ,COVID-19 Drug Treatment ,body regions ,Treatment Outcome ,030104 developmental biology ,Mutation ,Spike Glycoprotein, Coronavirus ,biology.protein ,Vero cell ,Female ,Antibody ,030217 neurology & neurosurgery ,Protein Binding - Abstract
COVID-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.
- Published
- 2021