Dual-action mechanism of viramidine functioning as a prodrug and as a catabolic inhibitor for ribavirin

Antimicrobial Agents and Chemotherapy
Jim Zhen WuZhi Hong

Abstract

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 microM. 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.

References

Mar 4, 1977·Annals of the New York Academy of Sciences·J P MillerJ Roboz
Jul 25, 2003·Antimicrobial Agents and Chemotherapy·Chin-Chung LinLi-Tain Yeh
Apr 24, 2004·Antimicrobial Agents and Chemotherapy·Chin-Chung LinLi-Tain Yeh

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Citations

Aug 23, 2011·Expert Opinion on Investigational Drugs·Paulina Deming, Sanjeev Arora
Jul 25, 2009·Clinics in Liver Disease·William W Shields, Paul J Pockros
Aug 10, 2005·Antiviral Research·Robert W SidwellD F Smee
Dec 2, 2008·Expert Opinion on Pharmacotherapy·Keith R KearneyVictor J Navarro
Oct 11, 2013·Drug Metabolism and Pharmacokinetics·Tomomi FurihataKan Chiba
Jun 2, 2016·Pharmacogenomics·Antonio D'AvolioGiovanni Di Perri
Aug 30, 2008·Antiviral Chemistry & Chemotherapy·Erik De Clercq, Hugh J Field

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