Ribavirin is a nucleoside analogue with broad antiviral activity. Here we report the synthesis and biological evaluation of novel ribavirin ProTides designed to deliver the bioactive ribavirin monophosphate into cells. Some of the compounds display activity similar to the parent nucleoside against a range of viruses. Enzymatic, cell lysate and preliminary modeling studies have been performed to...

BACKGROUND Serum HBV RNA is detectable during nucleoside/nucleotide analogue therapy as a result of unaffected RNA replicative intermediates or interrupted reverse transcription. We studied the predictive value of serum HBV RNA for initial virological response during nucleoside analogue therapy. METHODS Serum HBV RNA was quantified before and at 12 and 24 weeks of lamivudine or entecavir ther...

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Nucleoside analogues have proven to be a highly successful class of anti-cancer and anti-viral drugs. The therapeutic efficacy of nucleoside analogues is dependent of their intracellular phosphorylation. Two cellular nucleoside kinases, deoxycytidine kinase (dCK) and UMP-CMP kinase (CMK) are critical for phosphorylation of cytidine analogues. These kinases provide two first steps of activation ...

The phenylpropenamide derivatives AT-61 and AT-130 are nonnucleoside analogue inhibitors of hepatitis B virus (HBV) replication. They inhibited the replication of wild-type HBV with 50% inhibitory concentrations of 21.2 +/- 9.5 and 2.40 +/- 0.92 micro M, respectively, compared to 0.064 +/- 0.020 micro M lamivudine. There were no significant differences in sensitivity between wild-type and nucle...