A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes-Reference-Cited by-全球学者库

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

Published:2021-05-11 Issue:1 Volume:12 Page:
ISSN:2041-1723
Container-title:Nature Communications
language:en
Short-container-title:Nat Commun

Author:

Guo Yu^ORCID,Huang Lisu,Zhang Guangshun,Yao Yanfeng,Zhou He,Shen Shu^ORCID,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 Xingdong^ORCID,Lu Minmin,Li Yarong,Fang Yaohui,Lu Yun-Yueh,Hu Xue,Wang Shanshan,Zhang Wanju,Gao Ge,Adrian Francisco,Wang Qisheng^ORCID,Yu Feng,Peng Yun,Gabibov Alexander G.,Min Juan,Wang Yuhui,Huang Heyu,Stepanov Alexey^ORCID,Zhang Wei^ORCID,Cai Yan,Liu Junwei,Yuan Zhiming^ORCID,Zhang Chen,Lou Zhiyong^ORCID,Deng Fei^ORCID,Zhang Hongkai^ORCID,Shan Chao^ORCID,Schweizer Liang^ORCID,Sun Kun^ORCID,Rao Zihe^ORCID

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

Link

http://www.nature.com/articles/s41467-021-22926-2.pdf

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