Progress in the development of anti-hepatitis C virus nucleoside and nucleotide prodrugs

The search for new anti-hepatitis C virus (HCV) therapeutics continues as the current treatment, consisting of PEGylated IFN-alpha and ribavirin, is of limited efficacy, nonspecific and can cause significant side effects. Modified nucleoside analogues with improved efficacy and selectivity, may become the backbone of the future standard of care for anti-HCV therapies. Several families of modified nucleoside are known to inhibit HCV RNA-dependent RNA polymerase, a vital enzyme for viral replication. Ongoing efforts are focused on improvement of potency, selectivity and delivery of antiviral nucleoside analogues, with several recent promising advances into clinical trials. This review summarizes the current progress in the development of new anti-HCV nucleoside and nucleotide prodrugs.