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TITLE: Amantadine and Rimantadine Have No Direct Inhibitory
Effects against Hepatitis C Viral Protease, Helicase, ATPase,
Polymerase, and Internal Ribosomal Entry Site-Mediated
Translation.
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.
AUTHOR: Jubin R, Murray MG, Howe AY, Butkiewicz N, Hong Z,
Lau JY, Antiviral Therapy, Schering-Plough Research Institute,
Kenilworth, New Jersey, USA.
SOURCE: J Infect Dis 2000 Jan;181(1):331-334
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