ArticleAntimicrobial agents and chemotherapy2015
Hydroxylated tropolones inhibit hepatitis B virus replication by blocking viral ribonuclease H activity.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 87 citations in OpenAlex.
- Hepatitis B virus ribonuclease H inhibitors: Coming of age?Antiviral research · 2026Review
- The Evolution of Cell Culture Systems to Study Hepatitis B Virus Pathogenesis and Antiviral Susceptibility.Viruses · 2025Review
- Discovery of bimodal hepatitis B virus ribonuclease H and capsid assembly inhibitors.PLoS pathogens · 2025Article
- Article
- Identification and assessment of the 1,6-dihydroxy-pyridin-2-one moiety as privileged scaffold for HBV ribonuclease H inhibition.Antiviral research · 2024Article
- Catenulopyrizomicins, new anti-Hepatitis B virus compounds, from the rare actinomycete Catenuloplanes sp. MM782L-181F7.The Journal of antibiotics · 2024Article
- In Vitro Enzymatic and Cell Culture-Based Assays for Measuring Activity of HBV Ribonuclease H Inhibitors.Methods in molecular biology (Clifton, N.J.) · 2024Article
- In vitro evaluation of tropolone absorption, metabolism, and clearance.Antiviral research · 2023Article
- Targeting Ribonucleases with Small Molecules and Bifunctional Molecules.ACS chemical biology · 2023Review
- Antiviral Evaluation of Dispirotripiperazines against Hepatitis B Virus.Journal of medicinal chemistry · 2023Article
- Hepatitis B Virus Epsilon (ε) RNA Element: Dynamic Regulator of Viral Replication and Attractive Therapeutic Target.Viruses · 2023Review
- Targeting Metalloenzymes: The "Achilles' Heel" of Viruses and Parasites.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Article
- Carbocycloaddition Strategies for Troponoid Synthesis.Tetrahedron · 2023Article
- Predicted structure of the hepatitis B virus polymerase reveals an ancient conserved protein fold.Protein science : a publication of the Protein Society · 2022Article
- Alpha-hydroxytropolones are noncompetitive inhibitors of human RNase H1 that bind to the active site and modulate substrate binding.The Journal of biological chemistry · 2022Article
- Synthesis of Polyoxygenated Tropolones and their Antiviral Activity against Hepatitis B Virus and Herpes Simplex Virus-1.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- Effects of Troponoids on Mitochondrial Function and Cytotoxicity.Antimicrobial agents and chemotherapy · 2022Article
- Article
- Efficient Inhibition of Hepatitis B Virus (HBV) Replication and cccDNA Formation by HBV Ribonuclease H Inhibitors during Infection.Antimicrobial agents and chemotherapy · 2021Article
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
Hepatitis B virus (HBV) remains a major human pathogen despite the development of both antiviral drugs and a vaccine, in part because the current therapies do not suppress HBV replication far enough to eradicate the virus. Here, we screened 51 troponoid compounds for their ability to suppress HBV RNaseH activity and HBV replication based on the activities of α-hydroxytropolones against HIV RNaseH, with the goal of determining whether the tropolone pharmacophore may be a promising scaffold for anti-HBV drug development. Thirteen compounds inhibited HBV RNaseH, with the best 50% inhibitory concentration (IC50) being 2.3 μM. Similar inhibition patterns were observed against HBV genotype D and C RNaseHs, implying limited genotype specificity. Six of 10 compounds tested against HBV replication in culture suppressed replication via blocking of viral RNaseH activity, with the best 50% effective concentration (EC50) being 0.34 μM. Eighteen compounds inhibited recombinant human RNaseH1, and moderate cytotoxicity was observed for all compounds (50% cytotoxic concentration [CC50]=25 to 79 μM). Therapeutic indexes ranged from 3.8 to 94. Efficient inhibition required an intact α-hydroxytropolone moiety plus one or more short appendages on the tropolone ring, but a wide variety of constituents were permissible. These data indicate that troponoids and specifically α-hydroxytropolones are promising lead candidates for development as anti-HBV drugs, providing that toxicity can be minimized. Potential anti-RNaseH drugs are envisioned to be employed in combination with the existing nucleos(t)ide analogs to suppress HBV replication far enough to block genomic maintenance, with the goal of eradicating infection.
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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.