ArticlePloS one2013
Structure based identification and characterization of flavonoids that disrupt human papillomavirus-16 E6 function.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 87 citations in OpenAlex.
- Plant Bioactive Constituents and Their Potential Benefits in HPV-Positive Oropharyngeal Squamous Cell Carcinoma-A Narrative Review.Current issues in molecular biology · 2026Review
- Covalent inhibitors of human papillomavirus type 16 E6 protein restore p53 function and suppress growth of HPV-driven tumors in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Targeted degradation of the HPV oncoprotein E6 reduces tumor burden in cervical cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Article
- Human papilloma virus (HPV) mediated cancers: an insightful update.Journal of translational medicine · 2025Review
- In Silico Identification of Potential Antagonists Targeting the HPV16 E2-E1 Interaction: A Step Toward Novel Therapeutics for Cervical Cancer.Current issues in molecular biology · 2025Article
- Rational Design of Stapled Covalent Peptide Modifiers of Oncoprotein E6 from Human Papillomavirus.ACS chemical biology · 2025Article
- Anti-Epstein-Barr Virus Activities of Flavones and Flavonols with Effects on Virus-Related Cancers.Molecules (Basel, Switzerland) · 2025Review
- A Combination of Flavonoids Suppresses Cell Proliferation and the E6 Oncogenic Pathway in Human Papillomavirus-Transformed Cells.Pathogens (Basel, Switzerland) · 2025Article
- Discovering Active Chemotherapeutic Agents for Sexually Transmitted Diseases to Inhibit Pathogenic HPV-16-E6 Protein.Current drug discovery technologies · 2025Article
- Structure of the p53 degradation complex from HPV16.Nature communications · 2024Article
- Small Molecule Inhibitors of Human Papillomavirus: A Review of Research from 1997 to 2021.Current medicinal chemistry · 2024Review
- Discovery of reactive peptide inhibitors of human papillomavirus oncoprotein E6.Chemical science · 2023Article
- Targeting Mitochondrial Therapy in the Regulation of HPV Infection and HPV-Related Cancers.Pathogens (Basel, Switzerland) · 2023Review
- Prolidase-proline oxidase axis is engaged in apoptosis induction by birch buds flavonol santin in endometrial adenocarcinoma cell line.Frontiers in molecular biosciences · 2023Article
- Fermented Mangosteen (Cancers · 2022Article
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- Article
- Natural Bioactives: Back to the Future in the Fight against Human Papillomavirus? A Narrative Review.Journal of clinical medicine · 2022Review
- Activation of E6AP/UBE3A-Mediated Protein Ubiquitination and Degradation Pathways by a Cyclic γ-AA Peptide.Journal of medicinal chemistry · 2022Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
Expression and function of the human papillomavirus (HPV) early protein 6 (E6) is necessary for viral replication and oncogenesis in cervical cancers. HPV E6 targets the tumor suppressor protein p53 for degradation. To achieve this, "high-risk" HPV E6 proteins bind to and modify the target specificity of the ubiquitin ligase E6AP (E6 associated protein). This E6-dependent loss of p53 enables the virus to bypass host cell defenses and facilitates virally induced activation of the cell cycle progression during viral replication. Disruption of the interaction between E6 and E6AP and stabilization of p53 should decrease viability and proliferation of HPV positive cells. A new in vitro high-throughput binding assay was developed to assay binding between HPV-16 E6 and E6AP and to identify compounds that inhibit this interaction. The compound luteolin emerged from the screen and a library of novel flavones based on its structure was synthesized and characterized using this in vitro binding assay. The compounds identified in this study disrupt the E6/E6AP interaction, increase the levels of p53 and p21(Cip1/Waf1), and decrease proliferation of HPV positive cell lines. The new class of flavonoid E6 inhibitors displays a high degree of specificity for HPV positive cells. Docking analyses suggest that these compounds bind in a hydrophobic pocket at the interface between E6 and E6AP and mimic the leucines in the conserved α-helical motif of E6AP. The activity and specificity of these compounds represent a promising new lead for development as an antiviral therapy in the treatment of HPV infection and cervical cancer.
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