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ACE2-targeting monoclonal antibody as potent and broad-spectrum coronavirus blocker

文献类型：期刊论文

作者Chen, Yuning1,2; Zhang, Ya-Nan2,3; Yan, Renhong4,5; Wang, Guifeng1; Zhang, Yuanyuan4,5; Zhang, Zhe-Rui2,3; Li, Yaning6; Ou, Jianxia7; Chu, Wendi1,2; Liang, Zhijuan1,2
刊名SIGNAL TRANSDUCTION AND TARGETED THERAPY
出版日期2021-08-25
卷号6期号:1页码:9
ISSN号2095-9907
DOI10.1038/s41392-021-00740-y
通讯作者Zhou, Qiang(zhouqiang@westlake.edu.cn) ; Zhang, Bo(zhangbo@wh.iov.cn) ; Wang, Chunhe(wangc@simm.ac.cn)
英文摘要The evolution of coronaviruses, such as SARS-CoV-2, makes broad-spectrum coronavirus preventional or therapeutical strategies highly sought after. Here we report a human angiotensin-converting enzyme 2 (ACE2)-targeting monoclonal antibody, 3E8, blocked the S1-subunits and pseudo-typed virus constructs from multiple coronaviruses including SARS-CoV-2, SARS-CoV-2 mutant variants (SARS-CoV-2-D614G, B.1.1.7, B.1.351, B.1.617.1, and P.1), SARS-CoV and HCoV-NL63, without markedly affecting the physiological activities of ACE2 or causing severe toxicity in ACE2 "knock-in" mice. 3E8 also blocked live SARS-CoV-2 infection in vitro and in a prophylactic mouse model of COVID-19. Cryo-EM and "alanine walk" studies revealed the key binding residues on ACE2 interacting with the CDR3 domain of 3E8 heavy chain. Although full evaluation of safety in non-human primates is necessary before clinical development of 3E8, we provided a potentially potent and "broad-spectrum" management strategy against all coronaviruses that utilize ACE2 as entry receptors and disclosed an anti-coronavirus epitope on human ACE2.
WOS关键词ANGIOTENSIN-CONVERTING ENZYME-2 ; NEUTRALIZING ANTIBODIES ; RECEPTOR ; SPIKE ; ACE2 ; BINDING ; IDENTIFICATION ; PNEUMONIA
资助项目China National Major Scientific and Technological Special Project for Significant New Drugs Innovation and Development[2019ZX09732002006] ; Strategic Priority Research Program of the Chinese Academy of Sciences (CAS)[XDA12020223] ; Strategic Priority Research Program of the Chinese Academy of Sciences (CAS)[XDA12020330] ; National Natural Science Foundation of China[81872785] ; National Natural Science Foundation of China[81673347] ; National Natural Science Foundation of China[31971123] ; National Natural Science Foundation of China[32022037] ; National Natural Science Foundation of China[81920108015] ; National Natural Science Foundation of China[31930059] ; Shanghai Municipal Commission of Science and Technology of China[17431904400] ; Shanghai Municipal Commission of Science and Technology of China[19YF1457400] ; Institutes for Drug Discovery and Development, Chinese Academy of Sciences[CASIMM0120202008] ; Institutes for Drug Discovery and Development, Chinese Academy of Sciences[CASIMM0120202007] ; National Key RD Program[2020YFA0509303] ; Major Scientific and Technological Special Project of Zhongshan City[191022172638719] ; Major Scientific and Technological Special Project of Zhongshan City[210205143867019] ; Key R&D Program of Zhejiang Province[2020C04001] ; SARS-CoV-2 emergency project of the Science and Technology Department of Zhejiang Province[2020C03129] ; Leading Innovative and Entrepreneur Team Introduction Program of Hangzhou, Westlake Education Foundation ; Tencent Foundation
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology
语种英语
出版者SPRINGERNATURE
WOS记录号WOS:000688537400002
源URL[http://119.78.100.183/handle/2S10ELR8/297672]  
专题中国科学院上海药物研究所
通讯作者Zhou, Qiang; Zhang, Bo; Wang, Chunhe
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Biotherapeut Discovery Res Ctr, Shanghai, Peoples R China
2.Univ Chinese Acad Sci, Beijing, Peoples R China
3.Chinese Acad Sci, Wuhan Inst Virol, Key Lab Special Pathogens & Biosafety, Ctr Biosafety Mega Sci, Wuhan, Hubei, Peoples R China
4.Westlake Univ, Sch Life Sci, Key Lab Struct Biol Zhejiang Prov, Ctr Infect Dis Res,Westlake Lab Life Sci & Biomed, Hangzhou, Zhejiang, Peoples R China
5.Westlake Inst Adv Study, Inst Biol, Hangzhou, Zhejiang, Peoples R China
6.Tsinghua Univ, Sch Life Sci, Tsinghua Peking Joint Ctr Life Sci, Beijing Adv Innovat Ctr Struct Biol, Beijing, Peoples R China
7.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Jiangsu, Peoples R China
8.Dartsbio Pharmaceut, Zhongshan, Guangdong, Peoples R China
9.Nankai Univ, Drug Discovery Ctr Infect Dis, Tianjin, Peoples R China
10.Fudan Univ, Sch Pharm, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Chen, Yuning,Zhang, Ya-Nan,Yan, Renhong,et al. ACE2-targeting monoclonal antibody as potent and broad-spectrum coronavirus blocker[J]. SIGNAL TRANSDUCTION AND TARGETED THERAPY,2021,6(1):9.
APA Chen, Yuning.,Zhang, Ya-Nan.,Yan, Renhong.,Wang, Guifeng.,Zhang, Yuanyuan.,...&Wang, Chunhe.(2021).ACE2-targeting monoclonal antibody as potent and broad-spectrum coronavirus blocker.SIGNAL TRANSDUCTION AND TARGETED THERAPY,6(1),9.
MLA Chen, Yuning,et al."ACE2-targeting monoclonal antibody as potent and broad-spectrum coronavirus blocker".SIGNAL TRANSDUCTION AND TARGETED THERAPY 6.1(2021):9.

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来源：上海药物研究所

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