ArticleAntimicrobial agents and chemotherapy2012
Identification of disubstituted sulfonamide compounds as specific inhibitors of hepatitis B virus covalently closed circular DNA formation.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
116 citing papers in PubMed, 1 synthesis or guideline pooled it, 210 citations in OpenAlex.
- Hepatitis B infection and intrahepatic cholestasis of pregnancy: A systematic review and meta-analysis.Medicine · 2020Pooled it
- Rapid Turnover of Hepatitis B Virus Covalently Closed Circular DNA Indicated by Monitoring Emergence and Reversion of Signature-Mutation in Treated Chronic Hepatitis B Patients.Hepatology (Baltimore, Md.) · 2021Trial
- Covalently closed-circular hepatitis B virus DNA reduction with entecavir or lamivudine.World journal of gastroenterology · 2015Trial
- Cell-based platforms for antiviral screening against hepatitis B virus: advantages, limitations, and future perspectives.Antiviral research · 2026Review
- Orthogonal CRISPR screens and human liver chimeric mice identify hepatitis B virus host factors.bioRxiv : the preprint server for biology · 2026Article
- Lead Optimization of Xanthone Derivatives as Hepatitis B Virus cccDNA Reducers: Design, Synthesis, and Bioevaluation.ACS medicinal chemistry letters · 2026Article
- Identification of Marine-Derived Compounds with Potent Antiviral Activity in a Recombinant HBV cccDNA Cell Model.ACS omega · 2026Article
- Suppression of HBV replication and expression by CRISPR/Cas9 ribonucleoproteins.Antiviral research · 2026Article
- Host 3' flap endonuclease Mus81 plays a critical role in trimming the terminal redundancy of hepatitis B virus relaxed circular DNA during covalently closed circular DNA formation.PLoS pathogens · 2025Article
- Targeting HBV cccDNA Levels: Key to Achieving Complete Cure of Chronic Hepatitis B.Pathogens (Basel, Switzerland) · 2024Review
- Meeting report of the 37th International Conference on Antiviral Research in Gold Coast, Australia, May 20-24, 2024, organized by the International Society for Antiviral Research.Antiviral research · 2024Article
- Article
- NEDD4 family ubiquitin ligase AIP4 interacts with Alix to enable HBV naked capsid egress in an Alix ubiquitination-independent manner.PLoS pathogens · 2024Article
- Perspective on Emerging Therapies to Achieve Functional Cure of Chronic Hepatitis B.Current hepatology reports · 2024Article
- Tripartite Motif-Containing Protein 65 (TRIM65) Inhibits Hepatitis B Virus Transcription.Viruses · 2024Article
- Novel Approaches to Inhibition of HBsAg Expression from cccDNA and Chromosomal Integrants: A Review.Journal of clinical and translational hepatology · 2023Review
- Review
- Hepatitis B Virus Epsilon (ε) RNA Element: Dynamic Regulator of Viral Replication and Attractive Therapeutic Target.Viruses · 2023Review
- Synthetic gRNA/Cas9 ribonucleoprotein targeting HBV DNA inhibits viral replication.Journal of medical virology · 2023Article
- A RNase P Ribozyme Inhibits Gene Expression and Replication of Hepatitis B Virus in Cultured Cells.Microorganisms · 2023Article
56 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) plays a central role in viral infection and persistence and is the basis for viral rebound after the cessation of therapy, as well as the elusiveness of a cure even after extended treatment. Therefore, there is an urgent need for the development of novel therapeutic agents that directly target cccDNA formation and maintenance. By employing an innovative cell-based cccDNA assay in which secreted HBV e antigen is a cccDNA-dependent surrogate, we screened an in-house small-molecule library consisting of 85,000 drug-like compounds. Two structurally related disubstituted sulfonamides (DSS), termed CCC-0975 and CCC-0346, emerged and were confirmed as inhibitors of cccDNA production, with low micromolar 50% effective concentrations (EC(50)s) in cell culture. Further mechanistic studies demonstrated that DSS compound treatment neither directly inhibited HBV DNA replication in cell culture nor reduced viral polymerase activity in the in vitro endogenous polymerase assay but synchronously reduced the levels of HBV cccDNA and its putative precursor, deproteinized relaxed circular DNA (DP-rcDNA). However, DSS compounds did not promote the intracellular decay of HBV DP-rcDNA and cccDNA, suggesting that the compounds interfere primarily with rcDNA conversion into cccDNA. In addition, we demonstrated that CCC-0975 was able to reduce cccDNA biosynthesis in duck HBV-infected primary duck hepatocytes. This is the first attempt, to our knowledge, to identify small molecules that target cccDNA formation, and DSS compounds thus potentially serve as proof-of-concept drug candidates for development into therapeutics to eliminate cccDNA from chronic HBV 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.