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.
Keywords: Hepatits C, HCV, Nuclesides, Nucleotides, Phosphoramidates.
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