Niclosamide 니클로스아마이드 (Covid19, 코로나 치료제 후보)

 Niclosamide is an oral antihelminthic drug used to treat a large array of parasitic infections being included on the WHO list of essential medicines (150). In a screening of marketed drugs, it was identified to protect Vero E6 cells from the cytopathic effects of SARS‑CoV (151). Niclosamide inhibited SARS‑CoV replication in Vero E6 cells with a corresponding EC50 value under 0.1 μM, as measured by spike protein quantification (152). A yet not peer‑reviewed preprint presents the SARS‑CoV‑2 growth inhibition of niclosamide with an EC50 value of 0.17 μM. The authors proposed a mechanism of action that implicates the inhibition of SPK2 (143). SPK2 inhibitors reverse the reduction of BECN1 levels produced by SARS‑COV‑2 in host cells and enhance autophagy, inhibiting the viral replication (142,143). Another possible mechanism could be niclosamide's protonophore effect resulting in endosomal pH neutralization preventing acid‑dependent virus replication (153). The maximum plasma concentration after 500 mg x 3/day oral administration of niclosamide ranged from 35.7 to 182 ng/ml, equivalent to 0.1‑0.55 μM (154). The results showed poor oral bioavailability that could hinder immediate clinical utility against COVID‑ 19. The clinical trial NCT04372082 will evaluate niclosamide 500 mg x 4/day (day 1) followed by 500 mg x 2/day (days 2‑10) in combination with diltiazem 60 mg x 3/day (days 1‑10) (56). The use of diltiazem is supported by host‑targeted antiviral effects demonstrated in influenza mouse models (155).[지윤1] 

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 [지윤1]INTERNATIONAL JOURNAL OF molecular medicine 46: 467-488, 2020

 

 

Protonophore effect 로 인한 virus replication 억제

 

equivalent to 0.1‑0.55 μM효과범위

 

poor oral bioavailability that could hinder immediate clinical utility against COVID‑ 19.