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

Chen, Y.; Zhang, Y.; Yan, R.; Wang, G.; Zhang, Z.; Li, Y.; Chu, W.; Chen, G.; Wang, Q.; Zhou, Q.; Zhang, B.; Wang, C.

doi:10.1101/2020.11.11.375972

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bioRxiv · 10.1101/2020.11.11.375972

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

Chen, Y.·Zhang, Y.·Yan, R.·Wang, G.·Zhang, Z.·Li, Y.·Chu, W.·Chen, G.·Wang, Q.·Zhou, Q.·Zhang, B.·Wang, C.

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Abstract

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.

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Chen, Y., Zhang, Y., Yan, R., Wang, G., Zhang, Z., Li, Y., Chu, W., Chen, G., Wang, Q., Zhou, Q., Zhang, B., Wang, C.. 2020-11-12. ACE2-Targeting Monoclonal Antibody As A "Pan" Coronavirus Blocker In Vitro and In A Mouse Model. https://doi.org/10.1101/2020.11.11.375972

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