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

By Cheng Wang, Shaobo Wang, Daixi Li, Xia Zhao, Songling Han, Tao Wang, Gaomei Zhao, Yin Chen, Fang Chen, Jianqi Zhao, Liting Wang, Wei Sun, Yi Huang, Yongping Su, Dongqing Wei, Jinghong Zhao, Junping Wang

Posted 31 Mar 2020
bioRxiv DOI: 10.1101/2020.03.29.013490

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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