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ACE2-Targeting Monoclonal Antibody As A “Pan” Coronavirus Blocker In Vitro and In A Mouse Model

Yuning Chen, Yanan Zhang, Renhong Yan, Guifeng Wang, Yuanyuan Zhang, Zherui Zhang, Yaning Li, Wendi Chu, Yili Chen, Ganjun Chen, Qi Wang, Qiang Zhou, Bo Zhang, Chunhe Wang
doi: https://doi.org/10.1101/2020.11.11.375972
Yuning Chen
1Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200126, China
7University of Chinese Academy of Sciences, Beijing 100049, China
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Yanan Zhang
2Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei 430071, China
7University of Chinese Academy of Sciences, Beijing 100049, China
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Renhong Yan
3Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, and Institute of Biology, Westlake Institute for Advanced Study, 18 Shilongshan Road, Hangzhou, Zhejiang 310024, China
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Guifeng Wang
1Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200126, China
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Yuanyuan Zhang
3Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, and Institute of Biology, Westlake Institute for Advanced Study, 18 Shilongshan Road, Hangzhou, Zhejiang 310024, China
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Zherui Zhang
2Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei 430071, China
7University of Chinese Academy of Sciences, Beijing 100049, China
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Yaning Li
5Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China
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Wendi Chu
1Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200126, China
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Yili Chen
4Dartsbio Pharmaceuticals, Zhongshan, Guangdong 528400, China
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Ganjun Chen
4Dartsbio Pharmaceuticals, Zhongshan, Guangdong 528400, China
7University of Chinese Academy of Sciences, Beijing 100049, China
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Qi Wang
1Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200126, China
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Qiang Zhou
3Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, and Institute of Biology, Westlake Institute for Advanced Study, 18 Shilongshan Road, Hangzhou, Zhejiang 310024, China
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  • For correspondence: wangc@simm.ac.cn zhangbo@wh.iov.cn zhouqiang@westlake.edu.cn
Bo Zhang
2Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei 430071, China
6Drug Discovery Center for Infectious Disease, Nankai University, Tianjin 300350, China
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  • For correspondence: wangc@simm.ac.cn zhangbo@wh.iov.cn zhouqiang@westlake.edu.cn
Chunhe Wang
1Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200126, China
4Dartsbio Pharmaceuticals, Zhongshan, Guangdong 528400, China
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  • For correspondence: wangc@simm.ac.cn zhangbo@wh.iov.cn zhouqiang@westlake.edu.cn
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Abstract

Coronaviruses have caused three major outbreaks of infectious disease since the beginning of 21st century. Broad-spectrum strategies that can be utilized in both current and future coronavirus outbreaks and mutation-tolerant are sought after. Here we report a monoclonal antibody 3E8 targeting human angiotensin-converting enzyme 2 (ACE2) neutralized pseudo-typed coronaviruse SARS-CoV-2, SARS-CoV-2-D614G, SARS-CoV and HCoV-NL63, without affecting physiological activities of ACE2 or causing toxicity in mouse model. 3E8 also blocked live SARS-CoV-2 infection in vitro and in a mouse model of COVID-19. Cryo-EM studies revealed the binding site of 3E8 on ACE2 and identified Histone 34 of ACE2 as a critical site of anti-viral epitope. Overall, our work has provided a potential “pan” coronavirus management strategy and disclosed a “pan” anti-coronavirus epitope on human ACE2 for the first time.

Summary Blocking Multiple Coronaviruses by An ACE2-Neutralizing Monoclonal Antibody

Competing Interest Statement

Yi-Li Chen, Ganjun Chen and Chunhe Wang are employed by Dartsbio Pharmaceuticals

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted November 12, 2020.
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ACE2-Targeting Monoclonal Antibody As A “Pan” Coronavirus Blocker In Vitro and In A Mouse Model
Yuning Chen, Yanan Zhang, Renhong Yan, Guifeng Wang, Yuanyuan Zhang, Zherui Zhang, Yaning Li, Wendi Chu, Yili Chen, Ganjun Chen, Qi Wang, Qiang Zhou, Bo Zhang, Chunhe Wang
bioRxiv 2020.11.11.375972; doi: https://doi.org/10.1101/2020.11.11.375972
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ACE2-Targeting Monoclonal Antibody As A “Pan” Coronavirus Blocker In Vitro and In A Mouse Model
Yuning Chen, Yanan Zhang, Renhong Yan, Guifeng Wang, Yuanyuan Zhang, Zherui Zhang, Yaning Li, Wendi Chu, Yili Chen, Ganjun Chen, Qi Wang, Qiang Zhou, Bo Zhang, Chunhe Wang
bioRxiv 2020.11.11.375972; doi: https://doi.org/10.1101/2020.11.11.375972

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