ReviewAntiviral research2026
Hepatitis B virus ribonuclease H inhibitors: Coming of age?
Review in Antiviral research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Authors and funding
5 authors.
Funding
Abstract
Hepatitis B virus (HBV) replicates by reverse transcription in hepatocytes. It chronically infects >250 million people worldwide and kills ∼1.1 million annually. Current therapies for chronic HBV rely on nucleos(t)ide analogs as the front-line treatment or with pegylated interferon α. Neither type of therapy is curative, nucleos(t)ide analog therapy is usually life-long, and interferon α treatment causes substantial side effects. Therefore, novel therapies for HBV are urgently needed. The HBV ribonuclease H (RNase H) is one of the two viral enzymes needed for HBV reverse transcription, and it is not targeted by the existing HBV drugs. We have explored four chemotypes as HBV RNase H inhibitors, N-hydroxyisoquinolinediones (HID), α-hydroxytroplones (αHT), N-hydroxynapthyridinones (HNO), and N-hydroxypyridinediones (HPD). The HIDs and αHTs were terminated due to inability to improve efficacy and in vitro pharmacological liabilities, the HNOs have been de-emphasized due to limited efficacy, but the HPDs are under active development. The best HPDs have low nanomolar efficacies against HBV replication, selectivity indexes in culture of >1,000, and are synergistic with nucleos(t)ide analogs. Proof-of-principle in vivo efficacy has been demonstrated for an early HPD molecule, and the best HPDs are entering mouse efficacy, pharmacology, and toxicity studies. Here, we review the synthetic chemistry, efficacy, cytotoxicity, mechanism of action, effects on viral replication, and in vitro pharmacology of the HBV RNase H inhibitors. The goal is to develop drugs targeting the RNase H that could be used in combination with other drugs to achieve functional cures in people living the chronic HBV.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.