Abstract
At present, neither a selective antiviral therapy nor a vaccine is available for HCV, and the current treatment is only effective in a fraction of patients. Given the recent demonstration that antiviral compounds targeting the NS5B polymerase and the NS3/4A protease lead to rapid selection for resistance, iminosugar derivatives as HCV assembly inhibitors were characterized for drug resistance. It has been previously shown that deoxynojirimycin (DNJ)-containing iminosugars are potent HCV antivirals inhibiting ER alpha-glucosidases I and II. Long alkyl chain derivatives such asNN-DGJ inhibit the HCV p7 ion channel activityin vitro. The aim of this study was to characterize the drug resistance profile of an inhibitor targeting cellular enzymes (NB-DNJ) and of the p7 inhibitor NN-DGJ in comparison to the NS5B polymerase inhibitor 2’C-methyladenosine (2CMA).
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