Sofosbuvir Sovaldi The First-in-Class HCV NS5B Nucleotide Polymerase Inhibitor

Sofosbuvir (Sovaldi) The First-in-Class HCV NS5B Nucleotide Polymerase Inhibitor 

Currently, three categories of anti-HCV DAAs have been approved, and the nomenclature is based on which viral function is inhibited or affected. The categories are NS3/NS4A protease inhibitors [PI, e.g., boceprevir (2), telaprevir (3), and simeprevir (4)], NS5A protein inhibitors [e.g., ledipasvir (5)], and NS5B RNA-dependent RNA polymerase (RdRp) inhibitors (e.g., sofosbuvir). The last category can be divided further into two subclasses nucleoside/nucleotide polymerase inhibitors (NPI) and nonnucleoside polymerase inhibitors (NNPI). 

Innovative Drug Synthesis, First Edition. Edited by tie Jack Li and Douglas S Johnson. 2016 John Wiley Sons, Inc. Published 2016 by John Wiley Sons, Inc. 

In 1989, HCV was recognized and proven as the agent previously called non-A, non-B viral hepatitis (NANBH). In 1991, interferon became the first anti-HCV therapeutic approved by the US FDA and for the next 20 years ranained through several forms the backbone for HCV treatment. Approval of ribavirin in 1998 in combination with interferon (then PegIFN in 2001) improved efficacy bnt also added additional side effects.  

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