ArticleAntimicrobial agents and chemotherapy2013
Noncompetitive inhibition of hepatitis B virus reverse transcriptase protein priming and DNA synthesis by the nucleoside analog clevudine.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- A randomized phase 1b trial of the active site polymerase inhibitor nucleotide ATI-2173 in patients with chronic hepatitis B virus infection.Journal of viral hepatitis · 2023Trial
- Hepatitis B Virus Epsilon (ε) RNA Element: Dynamic Regulator of Viral Replication and Attractive Therapeutic Target.Viruses · 2023Review
- Recent Advances in Molecular Mechanisms of Nucleoside Antivirals.Current issues in molecular biology · 2023Review
- Management and Treatment of Patients with Chronic Hepatitis B: Towards Personalized Medicine.Viruses · 2022Review
- HIV-1-Mediated Acceleration of Oncovirus-Related Non-AIDS-Defining Cancers.Biomedicines · 2022Review
- Review of Current and Potential Treatments for Chronic Hepatitis B Virus Infection.Gastroenterology & hepatology · 2021Article
- Biogenesis and molecular characteristics of serum hepatitis B virus RNA.PLoS pathogens · 2020Article
- 3,7-Dihydroxytropolones Inhibit Initiation of Hepatitis B Virus Minus-Strand DNA Synthesis.Molecules (Basel, Switzerland) · 2020Article
- Potential Anti-SARS-CoV-2 Therapeutics That Target the Post-Entry Stages of the Viral Life Cycle: A Comprehensive Review.Viruses · 2020Review
- Article
- ATI-2173, a Novel Liver-Targeted Non-Chain-Terminating Nucleotide for Hepatitis B Virus Cure Regimens.Antimicrobial agents and chemotherapy · 2020Article
- HBV replication inhibitors.Antiviral research · 2020Review
- Development of Direct-acting Antiviral and Host-targeting Agents for Treatment of Hepatitis B Virus Infection.Gastroenterology · 2019Review
- In Vitro Anti-hepatitis B Virus Activity of 2',3'-Dideoxyguanosine.Virologica Sinica · 2018Article
- In Vitro Assays for RNA Binding and Protein Priming of Hepatitis B Virus Polymerase.Methods in molecular biology (Clifton, N.J.) · 2017Article
- Characterization of novel hepadnaviral RNA species accumulated in hepatoma cells treated with viral DNA polymerase inhibitors.Antiviral research · 2016Article
- Sodium selenite suppresses hepatitis B virus transcription and replication in human hepatoma cell lines.Journal of medical virology · 2016Article
- Hepatitis B virus reverse transcriptase - Target of current antiviral therapy and future drug development.Antiviral research · 2015Review
- Hepadnavirus Genome Replication and Persistence.Cold Spring Harbor perspectives in medicine · 2015Review
- Comparative analysis of hepatitis B virus polymerase sequences required for viral RNA binding, RNA packaging, and protein priming.Journal of virology · 2014Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
All currently approved antiviral drugs for the treatment of chronic hepatitis B virus (HBV) infection are nucleos(t)ide reverse transcriptase inhibitors (NRTI), which inhibit the DNA synthesis activity of the HBV polymerase. The polymerase is a unique reverse transcriptase (RT) that has a novel protein priming activity in which HP initiates viral DNA synthesis using itself as a protein primer. We have determined the ability of NRTI-triphosphates (TP) to inhibit HBV protein priming and their mechanisms of action. While entecavir-TP (a dGTP analog) inhibited protein priming initiated specifically with dGTP, clevudine-TP (a TTP analog) was able to inhibit protein priming independently of the deoxynucleoside triphosphate (dNTP) substrate and without being incorporated into DNA. We next investigated the effect of NRTIs on the second stage of protein priming, wherein two dAMP nucleotides are added to the initial deoxyguanosine nucleotide. The obtained results indicated that clevudine-TP as well as tenofovir DF-DP strongly inhibited the second stage of protein priming. Tenofovir DF-DP was incorporated into the viral DNA primer, whereas clevudine-TP inhibited the second stage of priming without being incorporated. Finally, kinetic analyses using the HBV endogenous polymerase assay revealed that clevudine-TP inhibited DNA chain elongation by HP in a noncompetitive manner. Thus, clevudine-TP appears to have the unique ability to inhibit HBV RT via binding to and distorting the HP active site, sharing properties with both NRTIs and nonnucleoside RT inhibitors.
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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.