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Lectin-like Intestinal Defensin Inhibits 2019-nCoV Spike binding to ACE2
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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.
Title: Lectin-like Intestinal Defensin Inhibits 2019-nCoV Spike binding to ACE2
Description:
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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