ArticleCellular and molecular gastroenterology and hepatology2019
Inhibition of HBV Transcription From cccDNA With Nitazoxanide by Targeting the HBx-DDB1 Interaction.
Article in Cellular and molecular gastroenterology and hepatology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 119 citations in OpenAlex.
- Dual HBV cccDNA-linked HiBiT reporter hepatocyte models for screening of candidate cccDNA modulators.Virulence · 2026Article
- Design, synthesis, characterization and exploration of anti-HBV activity of matrine-adenine hybrids.Molecular diversity · 2026Article
- Article
- Synthesis of Nitazoxanide Derivatives as Potent and Orally Available HBx-DDB1 Inhibitors against Hepatitis B Virus.ACS medicinal chemistry letters · 2026Article
- N6-methyladenosine modification in the context of viral infection: from molecular mechanism to therapeutic potential.Virus research · 2026Review
- HBx-Associated Reactivation of the IGF2 Locus in Chronic HBV Infection and HBV-Related Hepatocarcinogenesis: Evidence Boundaries and Biomarker Implications.Biomedicines · 2026Review
- Identification of Cyclin L1 as a Host Factor Regulating Hepatitis B Virus Replication.Viruses · 2026Article
- hnRNPA2B1 induces HBV cccDNA degradation by recruiting APOBEC3B.Nucleic acids research · 2026Article
- Review
- Innate immune recognition and evasion strategies of hepatitis B virus: from DNA to RNA and viral proteins.Frontiers in immunology · 2026Review
- Development of a CRE/CREB-driven HBx responsive HBV cell culture reporter system for antiviral drug evaluation.JHEP reports : innovation in hepatology · 2025Article
- Hepatitis B functional cure: Current and future perspective.World journal of hepatology · 2025Review
- Chronic Hepatitis B: Current Management and Future Directions.Diseases (Basel, Switzerland) · 2025Review
- Epigenetic drugs against human DNA viruses and retroviruses.Antiviral research · 2025Review
- Conserved Yet Divergent Smc5/6 Complex Degradation by Mammalian Hepatitis B Virus X Proteins.International journal of molecular sciences · 2025Article
- Structural basis of the hepatitis B virus X protein in complex with DDB1.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Design, Synthesis, and Bioevaluation of Matrine Derivatives as Potential Anti-Hepatitis B Virus Agents.Biomolecules · 2025Article
- Epigenetic regulation and its therapeutic potential in hepatitis B virus covalently closed circular DNA.Genes & diseases · 2025Review
- Targeting HBV cccDNA Levels: Key to Achieving Complete Cure of Chronic Hepatitis B.Pathogens (Basel, Switzerland) · 2024Review
- New thiourea derivatives that target the episomal silencing SMC5 protein to inhibit HBx-dependent viral DNA replication and gene transcription.Virusdisease · 2024Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsHepatitis B virus (HBV) infection is a major health concern worldwide. Although currently used nucleos(t)ide analogs efficiently inhibit viral replication, viral proteins transcribed from the episomal viral covalently closed circular DNA (cccDNA) minichromosome continue to be expressed long-term. Because high viral RNA or antigen loads may play a biological role during this chronicity, the elimination of viral products is an ultimate goal of HBV treatment. HBV regulatory protein X (HBx) was recently found to promote transcription of cccDNA with degradation of Smc5/6 through the interaction of HBx with the host protein DDB1. Here, this protein-protein interaction was considered as a new molecular target of HBV treatment.
methodsTo identify candidate compounds that target the HBx-DDB1 interaction, a newly constructed split luciferase assay system was applied to comprehensive compound screening. The effects of the identified compounds on HBV transcription and cccDNA maintenance were determined using HBV minicircle DNA, which mimics HBV cccDNA, and the natural HBV infection model of human primary hepatocytes.
resultsWe show that nitazoxanide (NTZ), a thiazolide anti-infective agent that has been approved by the FDA for protozoan enteritis, efficiently inhibits the HBx-DDB1 protein interaction. NTZ significantly restores Smc5 protein levels and suppresses viral transcription and viral protein production in the HBV minicircle system and in human primary hepatocytes naturally infected with HBV.
conclusionsThese results indicate that NTZ, which targets an HBV-related viral-host protein interaction, may be a promising new therapeutic agent and a step toward a functional HBV cure.
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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.