ArticleProceedings of the National Academy of Sciences of the United States of America2005
A heteroaryldihydropyrimidine activates and can misdirect hepatitis B virus capsid assembly.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers.
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Who cites it
139 citing papers in PubMed, 259 citations in OpenAlex.
- Systematic exploration of predicted quaternary structures within pandemic-relevant viral proteomes.bioRxiv : the preprint server for biology · 2026Article
- Negative cooperativity drives activity of capsid-directed antivirals against hepatitis B virus.Science advances · 2026Article
- Modeling Reveals How Direct-Acting Antivirals Redirect HBV Capsid Assembly Pathways to Noninfectious Products.bioRxiv : the preprint server for biology · 2026Article
- Many paths, similar destinations: viruses and bacterial microcompartments form polyhedra inside cells.Journal of virology · 2026Review
- Mechanistic insights into CAM-induced disruption of HBV capsids revealed by all-atom MD simulations.PLoS pathogens · 2026Article
- Design, Synthesis, and Biological Evaluation of Highly Potent Boronic Acid (Boronate Ester)-Bearing Heteroaryldihydropyrimidine Derivatives as HBV Capsid Assembly Modulators.Journal of medicinal chemistry · 2025Article
- Mechanistic insights into CAM-induced disruption of HBV capsids revealed by all-atom MD simulations.bioRxiv : the preprint server for biology · 2025Article
- Computer Simulations Show That Liquid-Liquid Phase Separation Enhances Self-Assembly.ACS nano · 2025Article
- Discovery of VNRX-9945, a Potent, Broadly Active Capsid Assembly Modulator as a Clinical Candidate for the Treatment of Chronic Hepatitis B Virus Infection.ACS medicinal chemistry letters · 2025Article
- Discovery and mechanism verification of first-in-class hydrophobic tagging-based degraders of HBV core protein.Acta pharmaceutica Sinica. B · 2025Article
- Induction of hepatitis B core protein aggregation targeting an unconventional binding site.eLife · 2025Article
- Mapping small molecule-RNA binding sites via Chem-CLIP synergized with capillary electrophoresis and nanopore sequencing.Nucleic acids research · 2025Article
- Review
- Small Molecule Assembly Agonist Alters the Dynamics of Hepatitis B Virus Core Protein Dimer and Capsid.Journal of the American Chemical Society · 2024Article
- Chemically Tagging Cargo for Specific Packaging inside and on the Surface of Virus-like Particles.ACS nano · 2024Article
- Antiviral Agents: Structural Basis of Action and Rational Design.Sub-cellular biochemistry · 2024Review
- 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
- Effect of ionic strength on the assembly of simian vacuolating virus capsid protein around poly(styrene sulfonate).The European physical journal. E, Soft matter · 2023Article
- Self-assembly coupled to liquid-liquid phase separation.PLoS computational biology · 2023Article
79 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Heteroaryldihydropyrimidines (HAPs) are a new class of antivirals inhibiting production of hepatitis B virus (HBV) virions in tissue culture. Here, we examine the effect of a representative HAP molecule, methyl 4-(2-chloro-4-fluorophenyl)-6-methyl-2-(pyridin-2-yl)-1,4-dihydropyrimidine-5-carboxylate (HAP-1), on the in vitro assembly of HBV capsid protein (Cp). HAP-1 enhances the rate and extent of Cp assembly over a broad concentration range. Aberrant particles, dominated by hexagonal arrays of Cp, were observed from assembly reactions with high HAP-1 concentrations. HAP-1 also led to dissociation of metastable HBV capsids, overcoming a kinetic barrier to dissociation by scavenging Cp and redirecting its assembly into hexamer-rich structures. Thus, HAP drugs act as allosteric effectors that induce an assembly-active state and, at high concentration, preferentially stabilize noncapsid polymers of Cp. HAP compounds may have multiple effects in vivo stemming from inappropriate assembly of Cp. These results show that activating and deregulating virus assembly may be a powerful general approach for antiviral therapeutics.
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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.