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

被引：47

作者：

Chen, Yuning ^{[1
,2
]}

Zhang, Ya-Nan ^{[2
,3
]}

Yan, Renhong ^{[4
,5
]}

Wang, Guifeng ^{[1
]}

Zhang, Yuanyuan ^{[4
,5
]}

Zhang, Zhe-Rui ^{[2
,3
]}

Li, Yaning ^{[6
]}

Ou, Jianxia ^{[7
]}

Chu, Wendi ^{[1
,2
]}

Liang, Zhijuan ^{[1
,2
]}

Wang, Yongmei ^{[1
,2
]}

Chen, Yi-Li

Chen, Ganjun ^{[8
]}

Wang, Qi

Zhou, Qiang ^{[4
,5
]}

Zhang, Bo ^{[3
,9
]}

Wang, Chunhe ^{[1
,2
,3
,7
,8
,10
]}

机构：

[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

来源：

SIGNAL TRANSDUCTION AND TARGETED THERAPY | 2021年 / 6卷 / 01期

基金：

中国国家自然科学基金;

关键词：

ANGIOTENSIN-CONVERTING ENZYME-2; NEUTRALIZING ANTIBODIES; SPIKE PROTEIN; RECEPTOR; ACE2; BINDING; IDENTIFICATION;

D O I：

10.1038/s41392-021-00740-y

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

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.

引用

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