Amantadine and rimantadine have no direct inhibitory effects against hepatitis C viral protease, helicase, ATPase, polymerase, and internal ribosomalentry site-mediated translation

Amantadine, a drug known to inhibit influenza A viral matrix (M2) protein f unction, was reported to be an effective treatment in some patients with ch ronic hepatitis C virus (HCV) infection. Sequence comparison shows no homol ogy between M2 and any of the HCV proteins. The effects of amantadine and a related analogue, rimantadine, on viral protease, helicase, ATPase, RNA-de pendent RNA polymerase, and HCV internal ribosomal entry site (IRES) transl ation were tested by established in vitro biochemical assays, No inhibition (>15%) of HCV protease, helicase, ATPase, and polymerase was observed with concentrations up to 400 mu g/mL. IRES-specific inhibition was not observe d at clinically relevant concentrations, but both cap and IRES reporter gen es were suppressed at higher levels, suggesting nonspecific translation inh ibition. In conclusion, amantadine and rimantadine have no direct and speci fic inhibitory effects against HCV protease, helicase, ATPase, polymerase, and IRES in vitro.