Amantadine and Rimantadine Have No Direct Inhibitory Effects against Hepatitis C Viral Protease, Helicase, ATPase, Polymerase, and Internal Ribosomal Entry Site-Mediated Translation.
Jubin R, Murray MG, Howe AY, Butkiewicz N, Hong Z, Lau JY
Antiviral Therapy, Schering-Plough Research Institute, Kenilworth, New Jersey,
J Infect Dis 2000 Jan;181(1):331-334
Amantadine, a drug known to inhibit influenza A viral matrix (M2) protein function, was reported to be an effective treatment in some patients with chronic hepatitis C virus (HCV) infection. Sequence comparison shows no homology between M2 and any of the HCV proteins. The effects of amantadine and a related analogue, rimantadine, on viral protease, helicase, ATPase, RNA-dependent RNA polymerase, and HCV internal ribosomal entry site (IRES) translation 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 mug/mL. IRES-specific inhibition was not observed at clinically relevant concentrations, but both cap and IRES reporter genes were suppressed at higher levels, suggesting nonspecific translation inhibition. In conclusion, amantadine and rimantadine have no direct and specific inhibitory effects against HCV protease, helicase, ATPase, polymerase, and IRES in vitro.