ArticlePLoS pathogens2017
HBV core protein allosteric modulators differentially alter cccDNA biosynthesis from de novo infection and intracellular amplification pathways.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 120 citations in OpenAlex.
- Precore mutation enhances viral replication to facilitate persistent infection especially in HBeAg-negative patients.Virologica Sinica · 2024Pooled it
- Efficacy, safety, and pharmacokinetics of capsid assembly modulator linvencorvir plus standard of care in chronic hepatitis B patients.Clinical and molecular hepatology · 2024Trial
- Mechanistic insights into CAM-induced disruption of HBV capsids revealed by all-atom MD simulations.PLoS pathogens · 2026Article
- Mechanisms underlying delayed loss of HBeAg and HBV DNA following HBsAg seroclearance in PEG-IFNα treated patients of chronic hepatitis B.Emerging microbes & infections · 2025Article
- Mechanistic insights into CAM-induced disruption of HBV capsids revealed by all-atom MD simulations.bioRxiv : the preprint server for biology · 2025Article
- Chronic Hepatitis B: Current Management and Future Directions.Diseases (Basel, Switzerland) · 2025Review
- HBV capsid assembly modulators differentially modulate the assembly of wild-type and drug-resistant core protein chimeric nucleocapsids and empty capsids.PLoS pathogens · 2025Article
- Article
- Review
- HBc: the multifunctional architect of HBV replication, immune evasion, and therapeutic innovation.Frontiers in immunology · 2025Review
- A nucleosome switch primes Hepatitis B Virus infection.bioRxiv : the preprint server for biology · 2024Article
- An allosteric inhibitor of sirtuin 2 blocks hepatitis B virus covalently closed circular DNA establishment and its transcriptional activity.Antiviral research · 2024Article
- Catenulopyrizomicins, new anti-Hepatitis B virus compounds, from the rare actinomycete Catenuloplanes sp. MM782L-181F7.The Journal of antibiotics · 2024Article
- A computational spatial whole-Cell model for hepatitis B viral infection and drug interactions.Scientific reports · 2023Article
- Recent Advances in the Development of Sulfamoyl-Based Hepatitis B Virus Nucleocapsid Assembly Modulators.Viruses · 2023Review
- Discovery of carboxyl-containing heteroaryldihydropyrimidine derivatives as novel HBV capsid assembly modulators with significantly improved metabolic stability.RSC medicinal chemistry · 2023Article
- Interferon-Free Regimens and Direct-Acting Antiviral Agents for Delta Hepatitis: Are We There Yet?Current issues in molecular biology · 2023Review
- Forthcoming Developments in Models to Study the Hepatitis B Virus Replication Cycle, Pathogenesis, and Pharmacological Advancements.ACS omega · 2023Review
- Hepatitis B Virus Capsid: The Core in Productive Entry and Covalently Closed Circular DNA Formation.Viruses · 2023Review
- Characterization of a Novel Capsid Assembly Modulator for the Treatment of Chronic Hepatitis B Virus Infection.Antimicrobial agents and chemotherapy · 2023Article
9 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 2 countries.
Funding
Abstract
Hepatitis B virus (HBV) core protein assembles viral pre-genomic (pg) RNA and DNA polymerase into nucleocapsids for reverse transcriptional DNA replication to take place. Several chemotypes of small molecules, including heteroaryldihydropyrimidines (HAPs) and sulfamoylbenzamides (SBAs), have been discovered to allosterically modulate core protein structure and consequentially alter the kinetics and pathway of core protein assembly, resulting in formation of irregularly-shaped core protein aggregates or "empty" capsids devoid of pre-genomic RNA and viral DNA polymerase. Interestingly, in addition to inhibiting nucleocapsid assembly and subsequent viral genome replication, we have now demonstrated that HAPs and SBAs differentially modulate the biosynthesis of covalently closed circular (ccc) DNA from de novo infection and intracellular amplification pathways by inducing disassembly of nucleocapsids derived from virions as well as double-stranded DNA-containing progeny nucleocapsids in the cytoplasm. Specifically, the mistimed cuing of nucleocapsid uncoating prevents cccDNA formation during de novo infection of hepatocytes, while transiently accelerating cccDNA synthesis from cytoplasmic progeny nucleocapsids. Our studies indicate that elongation of positive-stranded DNA induces structural changes of nucleocapsids, which confers ability of mature nucleocapsids to bind CpAMs and triggers its disassembly. Understanding the molecular mechanism underlying the dual effects of the core protein allosteric modulators on nucleocapsid assembly and disassembly will facilitate the discovery of novel core protein-targeting antiviral agents that can more efficiently suppress cccDNA synthesis and cure chronic hepatitis B.
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What OpenQuestion holds
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.