Virus infections are an increasing and probably lasting global risk. Nucleoside and nucleotide analogs represent the largest class of antiviral drugs. Early success in the treatment of human immunodeficiency virus infection and the recent approval of sofosbuvir as phosphoramidate nucleoside prodrug for chronic hepatitis C have provided proof of concept for important this class of compounds as an antiviral agent. This review summarizes the antiviral activity of nucleoside and nucleotide analogs and their recent application.

No abstract

No abstract

Pan-genotypic nucleoside HCV inhibitors display a high genetic barrier to drug resistance and are the preferred direct-acting agents to achieve complete sustained virologic response in humans. Herein, we report, the discovery of a β-d-2'-Cl,2'-F-uridine phosphoramidate nucleotide 16, as a nontoxic pan-genotypic anti-HCV agent. Phosphoramidate 16 in its 5'-triphosphate form specifically inhibited HCV NS5B polymerase with no marked inhibition of human polymerases and cellular mitochondrial RNA polymerase. Studies on the intracellular half-life of phosphoramidate 16-TP in live cells demonstrated favorable half-life of 11.6 h, suggesting once-a-day dosing. Stability in human blood and favorable metabolism in human intestinal microsomes and liver microsomes make phosphoramidate 16 a prospective candidate for further studies to establish its potential value as a new anti-HCV agent.