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

doi:10.1038/s41467-021-22926-2

	A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes
	Guo, Yu 1,2; Huang, Lisu 3; Zhang, Guangshun 1,2,4; Yao, Yanfeng 5; Zhou, He 6; Shen, Shu 7,8; Shen, Bingqing 6; Li, Bo 1,2,4; Li, Xin 1,2,4; Zhang, Qian 6; Chen, Mingjie 6; Chen, Da 1,2,4; Wu, Jia 6; Fu, Dan 1,2; Zeng, Xinxin 3; Feng, Mingfang 6; Pi, Chunjiang 6; Wang, Yuan 1,2,4; Zhou, Xingdong 1,2,4; Lu, Minmin 6; Li, Yarong 9; Fang, Yaohui 7,8; Lu, Yun-Yueh 6; Hu, Xue 7,8; Wang, Shanshan 6; Zhang, Wanju 3; Gao, Ge 5; Adrian, Francisco 6; Wang, Qisheng 10; Yu, Feng 10; Peng, Yun 5; Gabibov, Alexander G.11; Min, Juan 5; Wang, Yuhui 1,2,4; Huang, Heyu 3; Stepanov, Alexey 11; Zhang, Wei 1,2,4; Cai, Yan 12; Liu, Junwei 12; Yuan, Zhiming 5; Zhang, Chen 1,2; Lou, Zhiyong 13,14; Deng, Fei 7,8; Zhang, Hongkai1,2,4,15,16 ; Shan, Chao 7,8; Schweizer, Liang 6; Sun, Kun 3; Rao, Zihe 1,2,4,16,17
	2021
发表期刊	NATURE COMMUNICATIONS
ISSN	2041-1723
EISSN	2041-1723
卷号	12 期号:1
DOI	10.1038/s41467-021-22926-2
摘要	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. Antibodies against SARS-CoV-2 S protein can provide a treatment strategy for COVID-19. Here, Guo et al. provide the crystal structure of a SARS-CoV2 neutralizing antibody isolated from a convalescent patient and highlight the therapeutic efficacy in a rhesus monkey model of an engineered version with optimized pharmacokinetic and safety profile.
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收录类别	SCIE
语种	英语
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000658722500007
出版者	NATURE RESEARCH
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/127579
专题	免疫化学研究所_特聘教授组_张宏恺组
通讯作者	Guo, Yu; Lou, Zhiyong; Deng, Fei; Zhang, Hongkai; Shan, Chao; Schweizer, Liang; Sun, Kun; Rao, Zihe
作者单位	1.Nankai Univ, State Key Lab Med Chem Biol, Tianjin, Peoples R China; 2.Nankai Univ, Coll Pharm, Tianjin, Peoples R China; 3.Shanghai Jiao Tong Univ, Xinhua Hosp, Sch Med, Shanghai, Peoples R China; 4.Nankai Univ, Coll Life Sci, Tianjin, Peoples R China; 5.Chinese Acad Sci, Ctr Biosafety Megasci, Wuhan Inst Virol, Wuhan, Hubei, Peoples R China; 6.HiFiBio Hong Kong Ltd, Central, Hong Kong, Peoples R China; 7.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan, Hubei, Peoples R China; 8.Chinese Acad Sci, Wuhan Inst Virol, Natl Virus Resource Ctr, Wuhan, Hubei, Peoples R China; 9.Wuxi Biol Ltd, Shanghai, Peoples R China; 10.Chinese Acad Sci, Shanghai Adv Res Inst, Shanghai Synchrotron Radiat Facil, Shanghai, Peoples R China; 11.Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow, Russia; 12.Tianjin Int Joint Acad Biotechnol & Med, Tianjin, Peoples R China; 13.Tsinghua Univ, Sch Med, MOE Key Lab Prot Sci, Beijing, Peoples R China; 14.Tsinghua Univ, Sch Med, Collaborat Innovat Ctr Biotherapy, Beijing, Peoples R China; 15.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai, Peoples R China; 16.Nankai Univ, Frontiers Sci Ctr Cell Responses, Tianjin, Peoples R China; 17.Guangzhou Lab, Guangzhou, Guangdong, Peoples R China
通讯作者单位	免疫化学研究所
推荐引用方式 GB/T 7714	Guo, Yu,Huang, Lisu,Zhang, Guangshun,et al. A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes[J]. NATURE COMMUNICATIONS,2021,12(1).
APA	Guo, Yu.,Huang, Lisu.,Zhang, Guangshun.,Yao, Yanfeng.,Zhou, He.,...&Rao, Zihe.(2021).A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes.NATURE COMMUNICATIONS,12(1).
MLA	Guo, Yu,et al."A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes".NATURE COMMUNICATIONS 12.1(2021).