Usually, TThe antiviral strategies against SARS-CoV-2 includes prevention, interception and repair. Simutaneously, the entry of the virus into cell is via the interaction of the corona spike with ACE2. Furtheremore, Mpro activity is essential for virus replication in the cell. In additoon, Mpro, a virus protease, is a major potential molecular target for interception. Noticeably, Ebselen is a potent and orally active Mpro inhibitor (IC50= 0.67 μM) and inhibits SARS-CoV-2 virus (EC50=4.67 μM). Besides, Ebselen is a glutathione peroxidase mimetic, and a potent voltage-dependent calcium channel (VDCC) blocker. Ebselen is an organoselenium compound, can permeate the blood-brain barrier and has anti-inflammatory, antioxidant and anticancer activity.
Ebselen, an orally active Mpro inhibitor, can be used for virus infection research.
In vitro, Ebselen inhibits MoMuLV, HIV-1, and SIV with EC50s of 3.87 μM, 1.75 μM, 4.2 μM respevtively. Ebselen (10-100 μM; 20-24 h) shows strong antiviral effects in COVID-19 virus infected Vero cells. Ebselen (72 h) inhibits early viral postentry events of the HIV-1 life cycle with an EC50 of 1.99 μM in HeLa-CD4-LTR-LacZ cells.
In vivo, Ebselen (10 mg/kg, i.p.) alleviates testicular pathology in mice with Zika virus infection. More precisely, Ebselen reduces ZIKV-induced testicular oxidative stress, leucocyte infiltration, and production of pro-inflammatory response. Ebselen (10 mg/kg p.o. 3 h beforeinfection,daily for 3 days ) inhibits lung inflammation in an influenza A-induced lung inflammation mice model.
In conclusion, Ebselen is a Mpro inhibitor with potent antiviral effect. Therefore, Ebselen is potential in respiratory viral infections research.
References:
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[2] Thenin-Houssier S, et al. Antimicrob Agents Chemother. 2016 Mar 25;60(4):2195-208.
[3] Jin Z, et al. Nature. 2020 Jun;582(7811):289-293.