A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes

Yu Guo (), Lisu Huang, Guangshun Zhang, Yanfeng Yao, He Zhou, Shu Shen, Bingqing Shen, Bo Li, Xin Li, Qian Zhang, Mingjie Chen, Da Chen, Jia Wu, Dan Fu, Xinxin Zeng, Mingfang Feng, Chunjiang Pi, Yuan Wang, Xingdong Zhou, Minmin Lu, Yarong Li, Yaohui Fang, Yun-Yueh Lu, Xue Hu, Shanshan Wang, Wanju Zhang, Ge Gao, Francisco Adrian, Qisheng Wang, Feng Yu, Yun Peng, Alexander G. Gabibov, Juan Min, Yuhui Wang, Heyu Huang, Alexey Stepanov, Wei Zhang, Yan Cai, Junwei Liu, Zhiming Yuan, Chen Zhang, Zhiyong Lou (), Fei Deng (), Hongkai Zhang (), Chao Shan (), Liang Schweizer (), Kun Sun () and Zihe Rao ()
Additional contact information
Yu Guo: Nankai University
Lisu Huang: Shanghai Jiao Tong University School of Medicine
Guangshun Zhang: Nankai University
Yanfeng Yao: Wuhan Institute of Virology, Chinese Academy of Sciences
He Zhou: HiFiBio (Hong Kong) Limited
Shu Shen: Wuhan Institute of Virology, Chinese Academy of Sciences
Bingqing Shen: HiFiBio (Hong Kong) Limited
Bo Li: Nankai University
Xin Li: Nankai University
Qian Zhang: HiFiBio (Hong Kong) Limited
Mingjie Chen: HiFiBio (Hong Kong) Limited
Da Chen: Nankai University
Jia Wu: HiFiBio (Hong Kong) Limited
Dan Fu: Nankai University
Xinxin Zeng: Shanghai Jiao Tong University School of Medicine
Mingfang Feng: HiFiBio (Hong Kong) Limited
Chunjiang Pi: HiFiBio (Hong Kong) Limited
Yuan Wang: Nankai University
Xingdong Zhou: Nankai University
Minmin Lu: HiFiBio (Hong Kong) Limited
Yarong Li: Wuxi Biologics Limited
Yaohui Fang: Wuhan Institute of Virology, Chinese Academy of Sciences
Yun-Yueh Lu: HiFiBio (Hong Kong) Limited
Xue Hu: Wuhan Institute of Virology, Chinese Academy of Sciences
Shanshan Wang: HiFiBio (Hong Kong) Limited
Wanju Zhang: Shanghai Jiao Tong University School of Medicine
Ge Gao: Wuhan Institute of Virology, Chinese Academy of Sciences
Francisco Adrian: HiFiBio (Hong Kong) Limited
Qisheng Wang: Shanghai Advanced Research Institute, Chinese Academy of Sciences
Feng Yu: Shanghai Advanced Research Institute, Chinese Academy of Sciences
Yun Peng: Wuhan Institute of Virology, Chinese Academy of Sciences
Alexander G. Gabibov: Russian Academy of Sciences
Juan Min: Wuhan Institute of Virology, Chinese Academy of Sciences
Yuhui Wang: Nankai University
Heyu Huang: Shanghai Jiao Tong University School of Medicine
Alexey Stepanov: Russian Academy of Sciences
Wei Zhang: Nankai University
Yan Cai: Tianjin International Joint Academy of Biotechnology & Medicine
Junwei Liu: Tianjin International Joint Academy of Biotechnology & Medicine
Zhiming Yuan: Wuhan Institute of Virology, Chinese Academy of Sciences
Chen Zhang: Nankai University
Zhiyong Lou: Tsinghua University
Fei Deng: Wuhan Institute of Virology, Chinese Academy of Sciences
Hongkai Zhang: Nankai University
Chao Shan: Wuhan Institute of Virology, Chinese Academy of Sciences
Liang Schweizer: HiFiBio (Hong Kong) Limited
Kun Sun: Shanghai Jiao Tong University School of Medicine
Zihe Rao: Nankai University

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-22926-2

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