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.
D000248:Adenosine Kinase / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D009711:Nucleotides / Q000378:metabolism; D010766:Phosphorylation; D012136:Respiratory Syncytial Viruses; D010253:Respirovirus Infections / Q000378:metabolism*; D012254:Ribavirin / Q000378:metabolism*; D012263:Ribonucleosides / Q000378:metabolism*
D009711:Nucleotides; D012263:Ribonucleosides; D012254:Ribavirin; D000248:Adenosine Kinase