ArticleAntimicrobial agents and chemotherapy1998
In vitro inhibition of hepadnavirus polymerases by the triphosphates of BMS-200475 and lobucavir.
Article in Antimicrobial agents and chemotherapy, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 200 citations in OpenAlex.
- Entecavir for children and adults with chronic hepatitis B.The Cochrane database of systematic reviews · 2025Pooled it
- BaracleDrug design, development and therapy · 2017Trial
- Changes in Mitochondrial Toxicity in Peripheral Blood Mononuclear Cells During Four-Year Administration of Entecavir Monotherapy in Chinese Patients with Chronic Hepatitis B.Medical science monitor : international medical journal of experimental and clinical research · 2015Trial
- Two-year assessment of entecavir resistance in Lamivudine-refractory hepatitis B virus patients reveals different clinical outcomes depending on the resistance substitutions present.Antimicrobial agents and chemotherapy · 2007Trial
- Checkpoint-Dependent Sensitivities to Nucleoside Analogues Uncover Specific Patterns of Genomic Instability.Current issues in molecular biology · 2025Article
- Hepatitis B surface antigen: carcinogenesis mechanisms and clinical implications in hepatocellular carcinoma.Experimental hematology & oncology · 2025Review
- Nucleos(t)ide analogs for hepatitis B virus infection differentially regulate the growth factor signaling in hepatocytes.Hepatology communications · 2024Article
- Recent Advances in Molecular Mechanisms of Nucleoside Antivirals.Current issues in molecular biology · 2023Review
- Biochemical and Structural Properties of Entecavir-Resistant Hepatitis B Virus Polymerase with L180M/M204V Mutations.Journal of virology · 2021Article
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- Antiviral and Antimicrobial Nucleoside Derivatives: Structural Features and Mechanisms of Action.Molecular biology · 2021Article
- Remdesivir against COVID-19 and Other Viral Diseases.Clinical microbiology reviews · 2020Review
- Establishment of a novel hepatitis B virus culture system using immortalized human hepatocytes.Scientific reports · 2020Article
- Design, Synthesis and Bioactive Evaluation of Oxime Derivatives of Dehydrocholic Acid as Anti-Hepatitis B Virus Agents.Molecules (Basel, Switzerland) · 2020Article
- HBV Core Promoter Inhibition by Tubulin Polymerization Inhibitor (SRI-32007).Advances in virology · 2020Article
- Article
- CMCdG, a Novel Nucleoside Analog with Favorable Safety Features, Exerts Potent Activity against Wild-Type and Entecavir-Resistant Hepatitis B Virus.Antimicrobial agents and chemotherapy · 2019Article
- Development of Direct-acting Antiviral and Host-targeting Agents for Treatment of Hepatitis B Virus Infection.Gastroenterology · 2019Review
- HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir.Scientific reports · 2018Article
- Clinical characteristics of patients with chronic hepatitis B who developed genotypic resistance to entecavir: Real-life experience.Clinical and molecular hepatology · 2017Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The guanosine analogs BMS-200475 and lobucavir have previously been shown to effectively suppress propagation of the human hepatitis B virus (HBV) and woodchuck hepatitis virus (WHV) in 2.2.15 liver cells and in the woodchuck animal model system, respectively. This repression was presumed to occur via inhibition of the viral polymerase (Pol) by the triphosphate (TP) forms of BMS-200475 and lobucavir which are both produced in mammalian cells. To determine the exact mode of action, BMS-200475-TP and lobucavir-TP, along with several other guanosine analog-TPs and lamivudine-TP were tested against the HBV, WHV, and duck hepatitis B virus (DHBV) polymerases in vitro. Estimates of the 50% inhibitory concentrations revealed that BMS-200475-TP and lobucavir-TP inhibited HBV, WHV, and DHBV Pol comparably and were superior to the other nucleoside-TPs tested. More importantly, both analogs blocked the three distinct phases of hepadnaviral replication: priming, reverse transcription, and DNA-dependent DNA synthesis. These data suggest that the modest potency of lobucavir in 2.2.15 cells may be the result of poor phosphorylation in vivo. Kinetic studies revealed that BMS-200475-TP and lobucavir-TP competitively inhibit HBV Pol and WHV Pol with respect to the natural dGTP substrate and that both drugs appear to bind to Pol with very high affinities. Endogenous sequencing reactions conducted in replicative HBV nucleocapsids suggested that BMS-200475-TP and lobucavir-TP are nonobligate chain terminators that stall Pol at sites that are distinct yet characteristically two to three residues downstream from dG incorporation sites.
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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.