ArticleAntimicrobial agents and chemotherapy2005
Biphenylsulfonacetic acid inhibitors of the human papillomavirus type 6 E1 helicase inhibit ATP hydrolysis by an allosteric mechanism involving tyrosine 486.
Article in Antimicrobial agents and chemotherapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Targeted and untargeted metabolomics uncovering the effects of Jiawei Ermiao Granule on patients with persistent HPV infection.Frontiers in cellular and infection microbiology · 2025Article
- Small Molecule Inhibitors of Human Papillomavirus: A Review of Research from 1997 to 2021.Current medicinal chemistry · 2024Review
- Review
- Human Papillomavirus (HPV) Entry Inhibitors.Advances in experimental medicine and biology · 2022Article
- Leveraging Methylation Alterations to Discover Potential Causal Genes Associated With the Survival Risk of Cervical Cancer in TCGA Through a Two-Stage Inference Approach.Frontiers in genetics · 2021Article
- Review
- Article
- Identification of several high-risk HPV inhibitors and drug targets with a novel high-throughput screening assay.PLoS pathogens · 2017Article
- A Small Molecule Inhibitor Selectively Induces Apoptosis in Cells Transformed by High Risk Human Papilloma Viruses.PloS one · 2016Article
- Current progress in antiviral strategies.Trends in pharmacological sciences · 2014Review
- The E1 proteins.Virology · 2013Review
- Discovering new medicines targeting helicases: challenges and recent progress.Journal of biomolecular screening · 2013Review
- Targeting human papillomavirus genome replication for antiviral drug discovery.Antiviral therapy · 2013Review
- Analysis of the papillomavirus E2 and bromodomain protein Brd4 interaction using bimolecular fluorescence complementation.PloS one · 2013Article
- The E1 protein of human papillomavirus type 16 is dispensable for maintenance replication of the viral genome.Journal of virology · 2012Article
- Small molecule inhibitors of human papillomavirus protein - protein interactions.The open virology journal · 2011Article
- Recent advances in the search for antiviral agents against human papillomaviruses.Antiviral therapy · 2007Review
- Status Presens of Antiviral Drugs And Strategies: Part I: DNA Viruses and Retroviruses.Advances in antiviral drug design · 2007Review
Corrections and comments
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Authors and funding
7 authors.
Funding
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Abstract
Human papillomaviruses (HPVs) are the causative agents of benign and malignant lesions of the epithelium. Despite their high prevalence, there is currently no antiviral drug for the treatment of HPV-induced lesions. The ATPase and helicase activities of the highly conserved E1 protein of HPV are essential for viral DNA replication and pathogenesis and hence are considered valid antiviral targets. We recently described novel biphenylsulfonacetic acid inhibitors of the ATPase activity of E1 from HPV type 6 (HPV6). Based on kinetics and mutagenesis studies, we now report that these compounds act by an allosteric mechanism. They are hyperbolic competitive inhibitors of the ATPase activity of HPV6 E1 and also inhibit its helicase activity. Compounds in this series can also inhibit the ATPase activity of the closely related enzyme from HPV11; however, the most potent inhibitors of HPV6 E1 are significantly less active against the type 11 protein. We identified a single critical residue in HPV6 E1, Tyr-486, substituted by a cysteine in HPV11, which is primarily responsible for this difference in inhibitor potency. Interestingly, HPV18 E1, which also has a tyrosine at this position, could be inhibited by biphenylsulfonacetic acid derivatives, thereby raising the possibility that this class of inhibitors could be optimized as antiviral agents against multiple HPV types. These studies implicate Tyr-486 as a key residue for inhibitor binding and define an allosteric pocket on HPV E1 that can be exploited for future drug discovery efforts.
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