Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 48, Issue 10, Pages 4006-4008Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.48.10.4006-4008.2004
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An investigational nucleoside analogue drug, viramidine, has recently emerged as a potentially safer alternative to ribavirin for the treatment of hepatitis C viral infection. We have reported that viramidine mainly functions as a prodrug of ribavirin that is enriched in the liver. This in vitro study further explores viramidine's activity against nucleoside phosphorylase, a host enzyme that is responsible for phosphorolysis of ribavirin in vivo. Our experiments show that viramidine inhibits ribavirin phosphorolysis with a K-i of 2.5 muM. This result suggests that viramidine may act through a dual-action mechanism by serving as a prodrug of ribavirin and concomitantly as an inhibitor for nucleoside phosphorylase catabolism of ribavirin.
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