ArticleAntiviral research2018
Alkyl-imino sugars inhibit the pro-oncogenic ion channel function of human papillomavirus (HPV) E5.
Article in Antiviral research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 36 citations in OpenAlex.
- Review
- E5 Oncoprotein: A Key Player in Human Papillomavirus-Positive Head and Neck Cancer Pathogenesis and Therapy Resistance.Viruses · 2025Review
- HPV Infections-Classification, Pathogenesis, and Potential New Therapies.International journal of molecular sciences · 2024Review
- E7-mediated repression of miR-203 promotes LASP1-dependent proliferation in HPV-positive cervical cancer.Oncogene · 2024Article
- An Update on SARS-CoV-2 Clinical Trial Results-What We Can Learn for the Next Pandemic.International journal of molecular sciences · 2023Review
- Exploitation of ATP-sensitive potassium ion (KOncogene · 2023Article
- Characterization of the SARS-CoV-2 E Protein: Sequence, Structure, Viroporin, and Inhibitors.Protein science : a publication of the Protein Society · 2021Review
- E6-mediated activation of JNK drives EGFR signalling to promote proliferation and viral oncoprotein expression in cervical cancer.Cell death and differentiation · 2021Article
- The human papillomavirus oncoproteins: a review of the host pathways targeted on the road to transformation.The Journal of general virology · 2021Review
- Article
- Article
- HPV16 E5 Mediates Resistance to PD-L1 Blockade and Can Be Targeted with Rimantadine in Head and Neck Cancer.Cancer research · 2020Article
- Heterocyclic Inhibitors of Viroporins in the Design of Antiviral Compounds.Chemistry of heterocyclic compounds · 2020Article
- Iminosugars: Effects of Stereochemistry, Ring Size, andPharmaceuticals (Basel, Switzerland) · 2019Article
- Autocrine STAT3 activation in HPV positive cervical cancer through a virus-driven Rac1-NFκB-IL-6 signalling axis.PLoS pathogens · 2019Article
- Mucosal and Cutaneous Human Papillomavirus Infections and Cancer Biology.Frontiers in oncology · 2019Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Despite the availability of prophylactic vaccines the burden of human papillomavirus (HPV) associated malignancy remains high and there is a need to develop additional therapeutic strategies to complement vaccination. We have previously shown that the poorly characterised E5 oncoprotein forms a virus-coded ion channel or viroporin that was sensitive to the amantadine derivative rimantadine. We now demonstrate that alkylated imino sugars, which have antiviral activity against a number of viruses, inhibit E5 channel activity in vitro. Using molecular modelling we predict that imino sugars intercalate between E5 protomers to prevent channel oligomerisation. We explored the ability of these viroporin inhibitors to block E5-mediated activation of mitogenic signalling in keratinocytes. Treatment with either rimantadine or imino sugars prevented ERK-MAPK phosphorylation and reduced cyclin B1 expression in cells expressing E5 from a number of high-risk HPV types. Moreover, viroporin inhibitors also reduced ERK-MAPK activation and cyclin B1 expression in differentiating primary human keratinocytes containing high-risk HPV18. These observations provide evidence of a key role for E5 viroporin function during the HPV life cycle. Viroporin inhibitors could be utilised for stratified treatment of HPV associated tumours prior to virus integration, or as true antiviral therapies to eliminate virus prior to malignant transformation.
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