Alkyl-imino sugars inhibit the pro-oncogenic ion channel function of human papillomavirus (HPV) E5.

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

SUBMITTER: Wetherill LF 

PROVIDER: S-EPMC6156294 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature