The Chemistry of Anti-HCV Nucleosides and Pro-Nucleotides

Hepatitis C is a life threatening viral disease that commits millions of people worldwide. During the last decades, important developments in the understanding of the structural biology and biochemistry of the virus led to the development of direct acting antivirals culminating in the breakthrough development of the NS5B pronucleotide inhibitor Sofosbuvir which was approved by the FDA in 2013 to treat hepatits C. The advent of directing acting antivirals increased the sustained antiviral response from 38%-44% with peguilated interferon and ribavirin to 90-95% depending on the genotype. The path that led to Sofosbuvir passes through the development of important nucleosides such as 2`C-metil nucleosides and 2’-Me-2`F-2`-desoxi-nucleosides some of which achieved phase II clinical trials. The present work intends to review the developed chemistry that culminated in the abovementioned nucleosides as well as the chemistry of their pro-nucleotides phosphoramidates.