ArticleScientific reports2017
Heteroaryldihydropyrimidine (HAP) and Sulfamoylbenzamide (SBA) Inhibit Hepatitis B Virus Replication by Different Molecular Mechanisms.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
73 citing papers in PubMed.
- First-in-human study on the pharmacokinetics, safety, and tolerability of single escalating doses and multiple doses of XT1061, a novel core protein allosteric modulator, in healthy Chinese subjects.Frontiers in pharmacology · 2026Trial
- Safety, pharmacokinetics, and antiviral efficacy of the novel capsid assembly modulator GST-HG141 in patients with chronic hepatitis B: a phase 1 trial with a randomized, placebo-controlled design.Virology journal · 2024Trial
- Trial
- Negative cooperativity drives activity of capsid-directed antivirals against hepatitis B virus.Science advances · 2026Article
- Research progress of proteolysis-targeting chimeras in viral hepatitis drug discovery.Frontiers in chemistry · 2026Review
- Sophora alopecuroides biflavones glycoside, isolated from Sophora alopecuroides, inhibits the secretion of hepatitis B virus surface antigen through direct interaction with its antigenic loop domain.Virology journal · 2025Article
- HBV p22-interacting protein C1QBP inhibits viral replication through impeding nucleocapsid formation and nuclear import.PLoS pathogens · 2025Article
- The dynamic states of hepatitis B virus capsid monomers under the impact of different class of capsid-assembly modulators.Scientific reports · 2025Article
- HBV capsid assembly modulators differentially modulate the assembly of wild-type and drug-resistant core protein chimeric nucleocapsids and empty capsids.PLoS pathogens · 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
- Machine Learning of Molecular Dynamics Simulations Provides Insights into the Modulation of Viral Capsid Assembly.Journal of chemical information and modeling · 2025Article
- Discovery and mechanism verification of first-in-class hydrophobic tagging-based degraders of HBV core protein.Acta pharmaceutica Sinica. B · 2025Article
- Article
- Computer-aided drug repurposing & discovery for Hepatitis B capsid protein.In silico pharmacology · 2025Article
- Small Molecule Assembly Agonist Alters the Dynamics of Hepatitis B Virus Core Protein Dimer and Capsid.Journal of the American Chemical Society · 2024Article
- Conformationally Constrained Isoquinolinones as Orally Efficacious Hepatitis B Capsid Assembly Modulators.ACS medicinal chemistry letters · 2024Article
- Biophysics-Guided Lead Discovery of HBV Capsid Assembly Modifiers.ACS infectious diseases · 2024Article
- Recent Advances in the Development of Sulfamoyl-Based Hepatitis B Virus Nucleocapsid Assembly Modulators.Viruses · 2023Review
- Review
- Identification of novel tetrahydroquinoxaline derived phenyl ureas as modulators of the hepatitis B virus nucleocapsid assembly.European journal of medicinal chemistry · 2023Article
13 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
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heteroaryldihydropyrimidine (HAP) and sulfamoylbenzamide (SBA) are promising non-nucleos(t)ide HBV replication inhibitors. HAPs are known to promote core protein mis-assembly, but the molecular mechanism of abnormal assembly is still elusive. Likewise, the assembly status of core protein induced by SBA remains unknown. Here we show that SBA, unlike HAP, does not promote core protein mis-assembly. Interestingly, two reference compounds HAP_R01 and SBA_R01 bind to the same pocket at the dimer-dimer interface in the crystal structures of core protein Y132A hexamer. The striking difference lies in a unique hydrophobic subpocket that is occupied by the thiazole group of HAP_R01, but is unperturbed by SBA_R01. Photoaffinity labeling confirms the HAP_R01 binding pose at the dimer-dimer interface on capsid and suggests a new mechanism of HAP-induced mis-assembly. Based on the common features in crystal structures we predict that T33 mutations generate similar susceptibility changes to both compounds. In contrast, mutations at positions in close contact with HAP-specific groups (P25A, P25S, or V124F) only reduce susceptibility to HAP_R01, but not to SBA_R01. Thus, HAP and SBA are likely to have distinctive resistance profiles. Notably, P25S and V124F substitutions exist in low-abundance quasispecies in treatment-naïve patients, suggesting potential clinical relevance.
Indexed as
Identifiers
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.