File Entry: HCV NS3/4A 3 Protease Inhibitors: Simeprevir, Process Patents and Evaluation Krishnasarma Pathy*

In polymerase and protease drug targets and drug development, which has resulted in a strong infectious disease R&D portfolio,”
and has given the company its key pipeline asset, simeprevir (TMC435), a novel protease inhibitor in Phase III clinical
development for hepatitis C that is being developed in collaboration with Janssen Pharmaceuticals. Currently, hepatitis C virus
(HCV) infection is considered a serious health-care problem all over the world. A good number of direct-acting antivirals
(DAAs) against HCV infection are in clinical progress including NS3-4A protease inhibitors, RdRp, RNA-dependent RNA
polymerase inhibitors, and NS5A inhibitors as well as host targeted inhibitors. Two NS3-4A protease inhibitors (telaprevir
and boceprevir) have been recently approved for the treatment of hepatitis C in combination with standard of care (pegylated
interferon plus ribavirin). The new therapy has significantly improved sustained virologic response (SVR); however, the
adverse effects associated with this therapy are still the main concern. In addition to the emergence of viral resistance, other
targets must be continually developed. One such underdeveloped target is the helicase portion of the HCV NS3 protein. This
review article summarizes our current understanding of HCV treatment, particularly with those of NS3 inhibitors and patent
status and approvals of Simeprevir was clearly explained.