ArticleAntimicrobial agents and chemotherapy2007
A substituted tetrahydro-tetrazolo-pyrimidine is a specific and novel inhibitor of hepatitis B virus surface antigen secretion.
Article in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 94 citations in OpenAlex.
- Auranofin, identified by FDA-approved drug library screening, inhibits HBs antigen secretion via lysosomal damage.PloS one · 2026Article
- New tetrazolopyrrolidine-1,2,3-triazole analogues as potent anticancer agents: design, synthesis and molecular docking studies.Molecular diversity · 2024Article
- Pimobendan Inhibits HBV Transcription and Replication by Suppressing HBV Promoters Activity.Frontiers in pharmacology · 2022Article
- A novel piperazine derivative that targets hepatitis B surface antigen effectively inhibits tenofovir resistant hepatitis B virus.Scientific reports · 2021Article
- Establishment of stable cell lines in which the HBV genome replicates episomally for evaluation of antivirals.Archives of medical science : AMS · 2020Article
- Niacin analogue, 6-Aminonicotinamide, a novel inhibitor of hepatitis B virus replication and HBsAg production.EBioMedicine · 2019Article
- In water multicomponent synthesis of low-molecular-mass 4,7-dihydrotetrazolo[1,5-Beilstein journal of organic chemistry · 2019Article
- An Overview of Hepatitis B Virus Surface Antigen Secretion Inhibitors.Frontiers in microbiology · 2018Review
- Effective DABCO-catalyzed synthesis of new tetrazolo[1,5-a]pyrimidine analogs.Molecular diversity · 2017Article
- New Direct-Acting Antiviral Agents and Immunomodulators for Hepatitis B Virus Infection.Gastroenterology & hepatology · 2017Article
- The current status and future directions of hepatitis B antiviral drug discovery.Expert opinion on drug discovery · 2017Review
- Synthesis, effect of substituents on the regiochemistry and equilibrium studies of tetrazolo[1,5-Beilstein journal of organic chemistry · 2017Article
- Luteolin-7-Frontiers in microbiology · 2017Article
- Treatment of hepatitis B virus: an update.Future microbiology · 2016Review
- Prediction of HBF-0259 interactions with hepatitis B Virus receptors and surface antigen secretory factors.Virusdisease · 2016Article
- Eradication Strategies for Chronic Hepatitis B Infection.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2016Review
- Extract from Phyllanthus urinaria L. inhibits hepatitis B virus replication and expression in hepatitis B virus transfection model in vitro.Chinese journal of integrative medicine · 2015Article
- Chronic hepatitis B: A wave of new therapies on the horizon.Antiviral research · 2015Review
- The reactions of 2-ethoxymethylidene-3-oxo esters and their analogues with 5-aminotetrazole as a way to novel azaheterocycles.Beilstein journal of organic chemistry · 2015Article
- Therapeutic strategies for a functional cure of chronic hepatitis B virus infection.Acta pharmaceutica Sinica. B · 2014Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The high levels of hepatitis B virus (HBV) surface antigen (HBsAg)-bearing subviral particles in the serum of chronically infected individuals are thought to play a role in suppressing the HBV-specific immune response. Current therapeutics are not directed at reducing this viral antigenemia; thus, our group has focused on identifying inhibitors of HBsAg secretion. By using the HBV-expressing cell line HepG2.2.15, high-throughput screening of an 80,288-compound synthetic small-molecule library identified HBF-0259, an aromatically substituted tetrahydro-tetrazolo-(1, 5-a)-pyrimidine. Following resynthesis, HBF-0259 had a 50% effective concentration of approximately 1.5 microM in a secondary, HBV-expressing cell line, with a concentration that exhibited 50% cytotoxicity of >50 microM. The equilibrium concentration of HBF-0259 in aqueous solution at physiological pH was 15 to 16 microM; the selective index was thus >9. As intended by our screening paradigm, HBF-0259 is a selective, potent inhibitor of secretion of both subviral and DNA-containing viral particles, while the secretion of alpha-1-acid glycoprotein and alpha-1-antitrypsin was unaffected. The HBV e antigen, which is not a constituent of HBV particles, was also unaffected, suggesting that the secretion of particles bearing HBV structural glycoproteins is targeted directly. Inhibitory activity was also confirmed by transfection of HBsAg, indicating that the action of the compound is independent of those of other viral proteins. HBF-0259 had no effect on HBV DNA synthesis, demonstrating that inhibition is independent of viral genomic replication. Finally, HBF-0259 had little or no effect on the cell-to-cell spread of two unrelated viruses, suggesting that it is a specific inhibitor of secretion of HBsAg. Possible mechanisms of action and the implications for its development are discussed.
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