Conversion of Viramidine to Ribavirin <i>in Vivo</i> by Adenosine Deaminase and its Inhibition by 2′-Deoxycoformycin

Wu, Jim Zhen; Yeh, Li‐Tain; Lin, Chin‐Chung; Hong, Zhi

doi:10.1177/095632020601700105

Cited by 7 publications

(5 citation statements)

References 18 publications

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“…Valeant Pharmaceuticals International is developing taribavirin (Viramidine Ò , ribamidine) 68 for administration in combination with a pegylated interferon a-2b for the treatment of chronic HCV in treatment-naive patients. [239][240][241][242][243] Taribavirin is a prodrug of ribavirin 69, which is the standard treatment with interferon a-2b for HCV, as it is converted by adenosine deaminase to 69 in the liver. In 2006, Valeant released data from their Phase III trials (VISER1 and 2) showing that taribavirin 68 did not meet the non-inferiority efficacy endpoints.…”

Section: Antiviralmentioning

confidence: 99%

Natural products to drugs: natural product-derived compounds in clinical trials

2008

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Natural product and natural product-derived compounds that are being evaluated in clinical trials or are in registration (as at 31st December 2007) have been reviewed, as well as natural product-derived compounds for which clinical trials have been halted or discontinued since 2005. Also discussed are natural product-derived drugs launched since 2005, new natural product templates and late-stage development candidates.

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Section: Antiviralmentioning

confidence: 99%

Natural products to drugs: natural product-derived compounds in clinical trials

2008

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“…Viramidine (Fig. 3B) is an aminated prodrug of ribavirin that is deaminated in vivo by adenosine deaminase (Wu et al, 2006). The drug, following absorption, is rapidly converted to ribavirin .…”

Section: Ribavirin Analogues and Prodrugsmentioning

confidence: 99%

Molecular strategies to inhibit the replication of RNA viruses

2008

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There are virtually no antiviral drugs available for the treatment of infections with RNA viruses. This is particularly worrisome since most of the highly pathogenic and emerging viruses are, and will likely continue to be, RNA viruses. These viruses can cause acute, severe illness, including severe respiratory disease, hemorrhagic fever and encephalitis, with a high case fatality rate. It is important to have potent and safe drugs at hand that can be used for the treatment or prophylaxis of such infections. Drugs approved for the treatment of RNA virus infections (other than HIV) are the influenza M2 channel inhibitors, amantadine and rimantadine; the influenza neuraminidase inhibitors, oseltamivir and zanamivir, and ribavirin for the treatment of infections with respiratory syncytial virus and hepatitis C virus. The molecular mechanism(s) by which ribavirin inhibits viral replication, such as depletion of intracellular GTP pools and induction of error catastrophe, may not readily allow the design of analogues that are more potent/selective than the parent drug. Highly pathogenic RNA viruses belong to a variety of virus families, each having a particular replication strategy, thus offering a wealth of potential targets to selectively inhibit viral replication. We here provide a non-exhaustive review of potential experimental strategies, using small molecules, to inhibit the replication of several RNA viruses. Other approaches, such as the use of interferon or other host-response modifiers, immune serum or neutralizing antibodies, are not addressed in this review.

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“…Terabavirin is a ribavirin prodrug that is preferentially taken up by the liver. Inside the hepatocyte, terabavirin is converted to ribavirin by the enzyme adenosine deaminase (31). Ribavirin is then phosphorylated or may diffuse back into the circulation.…”

Section: Ribavirin Analoguesmentioning

confidence: 99%

What future for ribavirin?

Shiffman

2009

Liver International

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The optimal therapy for patients with the chronic hepatitis C virus (HCV) is a combination of peginterferon and ribavirin. Treating HCV without ribavirin or prematurely discontinuing, frequently missing doses of ribavirin is associated with a significant decline in virological response, and an increase in both breakthrough viraemia and relapse. The major limitation of ribavirin is adverse events, the most common of which is haemolytic anaemia. Haemolysis is modest when ribavirin is utilized as monotherapy, but is significantly increased when combined with interferon or peginterferon. For these reasons, attempts to replace ribavirin with a less toxic alternative have been advanced. Unfortunately, even when ribavirin is replaced by a potent protease inhibitor, relapse is significantly increased and SVR is reduced. The future of HCV treatment is to combine peginterferon and ribavirin with several protease and/or polymerase inhibitors. Whether this strategy will allow ribavirin to be removed from the treatment paradigm remains to be proven. However, based on the results of clinical trials conducted to date, it is much more likely that peginterferon, not ribavirin, could be expendable.

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Conversion of Viramidine to Ribavirin in Vivo by Adenosine Deaminase and its Inhibition by 2′-Deoxycoformycin

Cited by 7 publications

References 18 publications

Natural products to drugs: natural product-derived compounds in clinical trials

Natural products to drugs: natural product-derived compounds in clinical trials

Molecular strategies to inhibit the replication of RNA viruses

What future for ribavirin?

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