ArticleActa pharmacologica Sinica2014
Isothiafludine, a novel non-nucleoside compound, inhibits hepatitis B virus replication through blocking pregenomic RNA encapsidation.
Article in Acta pharmacologica Sinica, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 53 citations in OpenAlex.
- Yeast-Derived Glucan Particles: Biocompatibility, Efficacy, and Immunomodulatory Potential as Adjuvants and Delivery Systems.Pharmaceutics · 2025Article
- Psoralen inhibits hepatitis B viral replication by down-regulating the host transcriptional machinery of viral promoters.Virologica Sinica · 2022Article
- Review
- Current Progress in the Development of Hepatitis B Virus Capsid Assembly Modulators: Chemical Structure, Mode-of-Action and Efficacy.Molecules (Basel, Switzerland) · 2021Review
- [Clinical research progress of HBV RNA].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2020Article
- Natural Products: Review for Their Effects of Anti-HBV.BioMed research international · 2020Review
- 5-Aminothiophene-2,4-dicarboxamide analogues as hepatitis B virus capsid assembly effectors.European journal of medicinal chemistry · 2019Article
- Current landscape and future prospects of antiviral drugs derived from microbial products.The Journal of antibiotics · 2017Review
- Drugs in Development for Hepatitis B.Drugs · 2017Review
- A novel pyridazinone derivative inhibits hepatitis B virus replication by inducing genome-free capsid formation.Antimicrobial agents and chemotherapy · 2015Article
- Prevention of hepatitis B virus infection: from the past to the future.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2015Review
- Discovering novel anti-HCV compounds with inhibitory activities toward HCV NS3/4A protease.Acta pharmacologica Sinica · 2014Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo investigate the action of isothiafludine (NZ-4), a derivative of bis-heterocycle tandem pairs from the natural product leucamide A, on the replication cycle of hepatitis B virus (HBV) in vitro and in vivo.
methodsHBV replication cycle was monitored in HepG2.2.15 cells using qPCR, qRT-PCR, and Southern and Northern blotting. HBV protein expression and capsid assembly were detected using Western blotting and native agarose gel electrophoresis analysis. The interaction of pregenomic RNA (pgRNA) and the core protein was investigated by RNA immunoprecipitation. To evaluate the anti-HBV effect of NZ-4 in vivo, DHBV-infected ducks were orally administered NZ-4 (25, 50 or 100 mg·kg⁻¹·d⁻¹) for 15 d.
resultsNZ-4 suppressed intracellular HBV replication in HepG2.2.15 cells with an IC₅₀ value of 1.33 μmol/L, whereas the compound inhibited the cell viability with an IC₅₀ value of 50.4 μmol/L. Furthermore, NZ-4 was active against the replication of various drug-resistant HBV mutants, including 3TC/ETV-dual-resistant and ADV-resistant HBV mutants. NZ-4 (5, 10, 20 μmol/L) concentration-dependently reduced the encapsidated HBV pgRNA, resulting in the assembly of replication-deficient capsids in HepG2.2.15 cells. Oral administration of NZ-4 dose-dependently inhibited DHBV DNA replication in the DHBV-infected ducks.
conclusionNZ-4 inhibits HBV replication by interfering with the interaction between pgRNA and HBcAg in the capsid assembly process, thus increasing the replication-deficient HBV capsids. Such mechanism of action might provide a new therapeutic strategy to combat HBV infection.
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