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A Pangenotypic Hepatitis E Virus Replication Inhibitor With High Potency in a Rat Infection Model
Xin Zhang1, Mara Klöhn2, Sivi Ouwerkerk-Mahadevan3
1Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Virology, Antiviral Drug & Vaccine Research Group, KU Leuven, Leuven, Belgium.
Gastroenterology
|November 24, 2024
Summary
A new antiviral compound, JNJ-9117, shows promise for treating Hepatitis E virus (HEV) infections. It effectively reduced viral load in rats, even in combination with ribavirin, and has a good safety profile.
Area of Science:
- Hepatology
- Virology
- Drug Discovery
Background:
- Hepatitis E virus (HEV) causes significant global health issues, with millions infected annually.
- Current treatment options for HEV are limited, especially for immunocompromised individuals and pregnant women.
- There is a critical need for effective and safe antiviral therapies against HEV.
Purpose of the Study:
- To identify and evaluate novel antiviral agents for Hepatitis E virus (HEV) infection.
- To assess the efficacy and safety of compound JNJ-9117 as a potential HEV therapeutic.
- To explore combination therapy with existing antiviral drugs.
Main Methods:
- Screening of nucleoside analogues using HEV subgenomic replicon systems.
- In vitro antiviral activity testing in various cell culture models, including primary human hepatocytes.
- In vivo efficacy assessment in an established athymic nude rat model of chronic HEV infection.
Main Results:
- Compound JNJ-9117 demonstrated broad antiviral activity against multiple HEV genotypes in cell cultures.
- The drug exhibited a favorable pharmacokinetic and safety profile in preclinical rat studies.
- JNJ-9117 significantly reduced HEV RNA levels in rats, with enhanced efficacy when combined with ribavirin.
Conclusions:
- JNJ-9117 shows potential as a promising therapeutic agent for severe Hepatitis E virus infections.
- The compound's mechanism of action involves inhibiting viral RNA synthesis.
- Phase I human clinical trials have commenced to evaluate JNJ-9117 safety and tolerability.
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