Metabolism of ribavirin in respiratory syncytial virus-infected and uninfected cells

The metabolism of ribavirin to its mono-, di-, and triphosphate derivatives was examined in uninfected and respiratory syncytial virus-infected cells. The degree of phosphorylation was dose dependent upon extracellular ribavirin concentration. The major species formed was the triphosphate, with mono- and diphosphates being approximately 12 and 4% of the triphosphate, respectively. Amounts of triphosphate formed in infected cells were up to 2.6-fold greater than those in uninfected cells. Upon drug removal, ribavirin triphosphate degradation was very rapid, with decay half-lives of 70 to 100 min. Actinomycin D inhibited triphosphate production and also neutralized the antiviral effect of ribavirin.