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

• DOI: 10.1038/s41467-021-22926-2
• Publication Date: 2021-05-11T10:04:54Z
• Authors: 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; Zihe Rao
• Keywords: spike protein; Pandemic; 2019-20 coronavirus outbreak

Abstract COVID-19 pandemic caused by SARS-CoV-2 constitutes a global public health crisis with enormous economic consequences. Monoclonal antibodies against can provide an important treatment option to fight COVID-19, especially for the most vulnerable populations. In this work, potent binding Spike protein were identified from convalescent patients. Among them, P4A1 interacts directly and covers majority of Receptor Binding Motif Receptor-Binding Domain, shown high-resolution complex structure analysis. We further demonstrate neutralizing activities wild type mutant proteins or pseudoviruses. was subsequently engineered reduce potential risk Antibody-Dependent Enhancement infection extend its half-life. The antibody exhibits optimized pharmacokinetic safety profile, it results in complete viral clearance rhesus monkey model following single injection. These data suggest related diseases.