Antiviral Candidates for Treating Hepatitis E Virus Infection

Area of Science:

• Virology
• Drug Discovery
• Hepatology

Background:

• Hepatitis E virus (HEV) infection causes significant global health issues.
• Current treatments for HEV are limited, with existing options like ribavirin and alpha interferon having side effects and treatment failures.
• There is an urgent need for novel antiviral therapies against HEV.

Purpose of the Study:

• To identify and evaluate potential antiviral compounds for treating HEV infection.
• To explore drug repurposing as a strategy for developing new HEV antivirals.

Main Methods:

• Screened 16 nucleoside and non-nucleoside antiviral compounds against HEV genotype 1 replicon.
• Utilized luminescence studies and replicon RNA quantification to assess antiviral activity.
• Evaluated synergistic effects of combined drug treatments.

Main Results:

• Identified two potent HEV inhibitors: NITD008 (EC50, 0.03 μM) and GPC-N114 (EC50, 1.07 μM), both with low cytotoxicity (CC50 >100 μM).
• Both compounds significantly reduced HEV replicon RNA levels in cell culture.
• NITD008 and GPC-N114 demonstrated synergistic antiviral activity when used in combination.
• Sofosbuvir also showed efficacy against the HEV genotype 1 replicon (EC50, 1.97 μM).

Conclusions:

• Drug repurposing is a viable strategy for developing new hepatitis E virus (HEV) antivirals.
• NITD008 and GPC-N114 are promising candidates for further development as HEV therapeutics.
• Combination therapy with these agents may offer enhanced efficacy and reduced dosages.