title: Amantadine and rimantadine have no direct inhibitory effects against hepatitis C viral protease, helicase, ATPase, polymerase, and internal ribosomal entry site-mediated translation.
abstract: 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 microgram/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.
authors.affiliation: Antiviral Therapy, Schering-Plough Research Institute, Kenilworth, New Jersey, USA.
authors.forename: R
authors.initials: R
authors.lastname: Jubin
authors.forename: M G
authors.initials: MG
authors.lastname: Murray
authors.forename: A Y
authors.initials: AY
authors.lastname: Howe
authors.forename: N
authors.initials: N
authors.lastname: Butkiewicz
authors.forename: Z
authors.initials: Z
authors.lastname: Hong
authors.forename: J Y
authors.initials: JY
authors.lastname: Lau
mesh_terms: D000251:Adenosine Triphosphatases / Q000187:drug effects; D000547:Amantadine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D010450:Endopeptidases / Q000187:drug effects; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology; D014176:Protein Biosynthesis / Q000187:drug effects; D020365:RNA Helicases / Q000187:drug effects; D012324:RNA-Dependent RNA Polymerase / Q000187:drug effects; D012299:Rimantadine / Q000494:pharmacology*; D014763:Viral Matrix Proteins / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics; D000086082:Viroporin Proteins
chemical_list: D000251:Adenosine Triphosphatases; D000547:Amantadine; D010450:Endopeptidases; D020365:RNA Helicases; D012324:RNA-Dependent RNA Polymerase; D012299:Rimantadine; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C031540:M-protein, influenza virus; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins