From HCV to HEV: Repurposing a nucleoside analogue for hepatitis E therapy

Abstract

Section snippets

Background and context

Hepatitis E virus (HEV) infection is a substantial public health burden leading to approximately 20 million acute infections per year. The majority of infections are self-limiting, but relevant risks remain for pregnant women and immunocompromised patients, in whom HEV infection is associated with acute liver failure and chronic HEV infection, respectively.¹ HEV genotypes 1 (HEV-1) and 2 (HEV-2) are highly prevalent in low-income Asian and African countries, transmission occurs faecal-orally,

Objectives, methods and findings

The study by Zhang and colleagues investigated the antiviral effect of nucleoside analogues, originally developed against the hepatitis C virus (HCV), on HEV.⁸ Of the 19 different sugar-modified guanosine analogues tested, JNJ-9117 exhibited the most potent, broad-spectrum, in vitro antiviral activity against HEV-1, HEV-3, and rat HEV in various cell lines, including primary human hepatocytes and non-hepatic cell lines. Comparisons with ribavirin and sofosbuvir – an HCV polymerase inhibitor

Significance of findings

The study published by Zhang et al. demonstrates the in vitro and in vivo efficacy of JNJ-9117 in treating HEV infection, with a high resistance barrier and good tolerability in the animal model. JNJ-9117 was originally developed as a direct-acting antiviral to treat HCV infection, as it targets the viral polymerase. The imperative structural motifs of the catalytic site of the RdRp are comparable between HCV, HEV 1-4 and rat HEV, explaining the antiviral efficacy of JNJ-9117 in both HCV and

Financial support

The authors did not receive any financial support to produce this manuscript.

Conflict of interest

The authors of this study declare that they do not have any conflict of interest.Please refer to the accompanying ICMJE disclosure forms for further details.