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

页数：9

共 43 条

[21] Molecular basis of cross-species ACE2 interactions with SARS-CoV-2-like viruses of pangolin origin [J].

Niu, Sheng ;

Wang, Jia ;

Bai, Bin ;

Wu, Lili ;

Zheng, Anqi ;

Chen, Qian ;

Du, Pei ;

Han, Pengcheng ;

Zhang, Yanfang ;

Jia, Yunfei ;

Qiao, Chengpeng ;

Qi, Jianxun ;

Tian, Wen-xia ;

Wang, Hong-Wei ;

Wang, Qihui ;

Gao, George Fu .

EMBO JOURNAL, 2021, 40 (16)

[22] SARS-coronavirus modulation of myocardial ACE2 expression and inflammation in patients with SARS [J].

Oudit, G. Y. ;

Kassiri, Z. ;

Jiang, C. ;

Liu, P. P. ;

Poutanen, S. M. ;

Penninger, J. M. ;

Butany, J. .

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 2009, 39 (07) :618-625

[23] Cross-neutralization ofSARS-CoV-2 by a human monoclonal SARS-CoV antibody [J].

Pinto, Dora ;

Park, Young-Jun ;

Beltramello, Martina ;

Walls, Alexandra C. ;

Tortorici, M. Alejandra ;

Bianchi, Siro ;

Jaconi, Stefano ;

Culap, Katja ;

Zatta, Fabrizia ;

De Marco, Anna ;

Peter, Alessia ;

Guarino, Barbara ;

Spreafico, Roberto ;

Cameroni, Elisabetta ;

Case, James Brett ;

Chen, Rita E. ;

Havenar-Daughton, Colin ;

Snell, Gyorgy ;

Telenti, Amalio ;

Virgin, Herbert W. ;

Lanzavecchia, Antonio ;

Diamond, Michael S. ;

Fink, Katja ;

Veesler, David ;

Corti, Davide .

NATURE, 2020, 583 (7815) :290-+

[24] Spike mutation D614G alters SARS-CoV-2 fitness [J].

Plante, Jessica A. ;

Liu, Yang ;

Liu, Jianying ;

Xia, Hongjie ;

Johnson, Bryan A. ;

Lokugamage, Kumari G. ;

Zhang, Xianwen ;

Muruato, Antonio E. ;

Zou, Jing ;

Fontes-Garfias, Camila R. ;

Mirchandani, Divya ;

Scharton, Dionna ;

Bilello, John P. ;

Ku, Zhiqiang ;

An, Zhiqiang ;

Kalveram, Birte ;

Freiberg, Alexander N. ;

Menachery, Vineet D. ;

Xie, Xuping ;

Plante, Kenneth S. ;

Weaver, Scott C. ;

Shi, Pei-Yong .

NATURE, 2021, 592 (7852) :116-121

[25] Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody [J].

Rappazzo, C. Garrett ;

Tse, Longping, V ;

Kaku, Chengzi, I ;

Wrapp, Daniel ;

Sakharkar, Mrunal ;

Huang, Deli ;

Deveau, Laura M. ;

Yockachonis, Thomas J. ;

Herbert, Andrew S. ;

Battles, Michael B. ;

O'Brien, Cecilia M. ;

Brown, Michael E. ;

Geoghegan, James C. ;

Belk, Jonathan ;

Peng, Linghang ;

Yang, Linlin ;

Hou, Yixuan ;

Scobey, Trevor D. ;

Burton, Dennis R. ;

Nemazee, David ;

Dye, John M. ;

Voss, James E. ;

Gunn, Bronwyn M. ;

McLellan, Jason S. ;

Baric, Ralph S. ;

Gralinski, Lisa E. ;

Walker, Laura M. .

SCIENCE, 2021, 371 (6531) :823-+

[26]

Santos R. A. S., 2005, Current Medicinal Chemistry - Cardiovascular & Hematological Agents, V3, P383, DOI 10.2174/156801605774322373

[27]

Shen Xiaoying, 2021, Cell Host Microbe, V29, P529, DOI [10.1016/j.chom.2021.03.002, 10.1101/2021.01.27.428516]

[28] Intranasal gene therapy to prevent infection by SARS-CoV-2 variants [J].

Sims, Joshua J. ;

Greig, Jenny A. ;

Michalson, Kristofer T. ;

Lian, Sharon ;

Martino, R. Alexander ;

Meggersee, Rosemary ;

Turner, Kevin B. ;

Nambiar, Kalyani ;

Dyer, Cecilia ;

Hinderer, Christian ;

Horiuchi, Makoto ;

Yan, Hanying ;

Huang, Xin ;

Chen, Shu-Jen ;

Wilson, James M. .

PLOS PATHOGENS, 2021, 17 (07)

[29] Genomic mutations and changes in protein secondary structure and solvent accessibility of SARS-CoV-2 (COVID-19 virus) [J].

Thanh Thi Nguyen ;

Pathirana, Pubudu N. ;

Thin Nguyen ;

Quoc Viet Hung Nguyen ;

Bhatti, Asim ;

Nguyen, Dinh C. ;

Dung Tien Nguyen ;

Ngoc Duy Nguyen ;

Creighton, Douglas ;

Abdelrazek, Mohamed .

SCIENTIFIC REPORTS, 2021, 11 (01) :3487

[30] ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis [J].

Towler, P ;

Staker, B ;

Prasad, SG ;

Menon, S ;

Tang, J ;

Parsons, T ;

Ryan, D ;

Fisher, M ;

Williams, D ;

Dales, NA ;

Patane, MA ;

Pantoliano, MW .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (17) :17996-18007

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