The story of ribavirin (1--D-ribofuranosyl-1, 2, 4-triazole-3-carboxamide), a purine nucleoside analogue, began when Drs. Joseph T. Witkowski and Roland K. Robins synthesized the compound in 1970. 1 The broadspectrum antiviral activity was reported in 1972. 2 The aerosol form of ribavirin was approved for the treatment of respiratory syncytial virus infection in children with respiratory distress in mid-1980, before the discovery of hepatitis C virus (HCV) reported in 1989. 3 The ribavirin/interferon alpha (IFN-) combination therapy was approved by the United States Regulatory Authorities in 1998. Three decades of research efforts, including the life-long effort of a number of unsung scientists, finally allowed ribavirin to establish its position in the history of medicine.

The success of ribavirin/IFN-combination therapy for chronic HCV infection, a viral infection affecting 170 million people worldwide, has provoked a renewed and intense effort to further explore the mechanism (s) of action of ribavirin, with the belief that such information will guide the design of better therapies against HCV. Such a task is not straightforward. IFN-has been shown to possess direct antiviral, antiproliferative, and immunomodulatory activities. The mechanistic pathways in-