Lectin-like Intestinal Defensin Inhibits 2019-nCoV Spike binding to ACE2

Wang, C.; Wang, S.; Li, D.; Zhao, X.; Han, S.; Wang, T.; Zhao, G.; Chen, Y.; Chen, F.; Zhao, J.; Wang, L.; Sun, W.; Huang, Y.; Su, Y.; Wei, D.; Wang, J.

doi:10.1101/2020.03.29.013490

bioRxiv · 10.1101/2020.03.29.013490

Lectin-like Intestinal Defensin Inhibits 2019-nCoV Spike binding to ACE2

Wang, C.·Wang, S.·Li, D.·Zhao, X.·Han, S.·Wang, T.·Zhao, G.·Chen, Y.·Chen, F.·Zhao, J.·Wang, L.·Sun, W.·Huang, Y.·Su, Y.·Wei, D.·Wang, J.

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Abstract

The burgeoning epidemic caused by novel coronavirus 2019 (2019-nCoV) is currently a global concern. Angiotensin-converting enzyme-2 (ACE2) is a receptor of 2019-nCoV spike 1 protein (S1) and mediates viral entry into host cells. Despite the abundance of ACE2 in small intestine, few digestive symptoms are observed in patients infected by 2019-nCoV. Herein, we investigated the interactions between ACE2 and human defensins (HDs) specifically secreted by intestinal Paneth cells. The lectin-like HD5, rather than HD6, bound ACE2 with a high affinity of 39.3 nM and weakened the subsequent recruitment of 2019-nCoV S1. The cloak of HD5 on the ligand-binding domain of ACE2 was confirmed by molecular dynamic simulation. A remarkable dose-dependent preventive effect of HD5 on 2019-nCoV S1 binding to intestinal epithelial cells was further evidenced by in vitro experiments. Our findings unmasked the innate defense function of lectin-like intestinal defensin against 2019-nCoV, which may provide new insights into the prevention and treatment of 2019-nCoV infection.

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Wang, C., Wang, S., Li, D., Zhao, X., Han, S., Wang, T., Zhao, G., Chen, Y., Chen, F., Zhao, J., Wang, L., Sun, W., Huang, Y., Su, Y., Wei, D., Wang, J.. 2020-03-31. Lectin-like Intestinal Defensin Inhibits 2019-nCoV Spike binding to ACE2. https://doi.org/10.1101/2020.03.29.013490

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