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

By 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

Posted 12 Nov 2020
bioRxiv DOI: 10.1101/2020.11.11.375972

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. ### Competing Interest Statement Yi-Li Chen, Ganjun Chen and Chunhe Wang are employed by Dartsbio Pharmaceuticals

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