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; jianxia ou; Wendi Chu; Zhijuan Liang; yongmei wang; Yili Chen; Ganjun Chen; Qi Wang; Qiang Zhou; Bo Zhang; Chunhe Wang

This article is a Preprint

Preprints are preliminary research reports that have not been certified by peer review. They should not be relied on to guide clinical practice or health-related behavior and should not be reported in news media as established information.

Preprints posted online allow authors to receive rapid feedback and the entire scientific community can appraise the work for themselves and respond appropriately. Those comments are posted alongside the preprints for anyone to read them and serve as a post publication assessment.

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; jianxia ou; Wendi Chu; Zhijuan Liang; yongmei wang; Yili Chen; Ganjun Chen; Qi Wang; Qiang Zhou; Bo Zhang; Chunhe Wang.

Yuning Chen; Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200126, China.
Yanan Zhang; Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei 430
Renhong Yan; Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School
Guifeng Wang; Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200126, China.
Yuanyuan Zhang; Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School
Zherui Zhang; Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei 430
Yaning Li; Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing
jianxia ou; School of Chinese Materia Medica, Nanjing University of Chinese Medicine
Wendi Chu; Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200126, China.
Zhijuan Liang; Shanghai Institute of Materia Medica
yongmei wang; Shanghai Institute of Materia Medica
Yili Chen; Dartsbio Pharmaceuticals, Zhongshan, Guangdong 528400, China
Ganjun Chen; Dartsbio Pharmaceuticals, Zhongshan, Guangdong 528400, China
Qi Wang; Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200126, China.
Qiang Zhou; Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School
Bo Zhang; Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei 430
Chunhe Wang; Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200126, China.

Preprint En | PREPRINT-BIORXIV | ID: ppbiorxiv-375972

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.

cc_no

XML