Abstract
Infection with Hepatitis C Virus (HCV) is a major health problem affecting 270 million people worldwide and 10 million people in Pakistan. Currently, there is no vaccine available for prevention of HCV infection due to the high degree of strain variation. The current standard of care is a combination of Pegylated interferon ? (PEG-INF ?) with ribavirin and Boceprevir/Telaprevir. Hence, there is a need to develop new antiviral agents from different targets. HCV NS3, a nonstructural protein has serine/protease and helicase domain, and these domains are considered as important antiviral drug targets to combat HCV. In the past 15 years, major scientific advances have enabled the development of many novel serine/protease and helicase inhibitors by using in vivo as well as in vitro model systems. Most of NS3 protease inhibitors have entered in different clinical trials phases but still there is a need to improve the functionality of these inhibitory compounds. This review summarizes potent antiviral compounds against HCV NS3 protease and their activity in combination with standard therapy. In conclusion, it will be very exciting to see HCV NS3-4A serine protease/helicase inhibitors progress through clinical developments and, hopefully, provide hepatitis C patients with much needed, more effective therapies.
Highlights
Hepatitis C Virus (HCV) represents a global health concern as it is responsible for a significant number of hepatitis cases worldwide [1]
Two NS3 protease inhibitors Bocepreir and Telaprevir have been approved as a standard of care for HCV genotype 1 patients and can be used with triple therapy (PEG-IFN- α, ribavirin and Boceprevir or Telaprevir) [9]
Introduction of various modified prolines at P2 and optimization of the P1 side chain led into the discovery of SCH6 (SCH446211) [27], which is a ketoamide peptidomimetic inhibitor that showed potent inhibition of HCV NS3/4A protease in vitro with an extended interaction in Huh7 hepatoma cells stably transfected with a subgenomic HCV RNA replicon
Summary
HCV represents a global health concern as it is responsible for a significant number of hepatitis cases worldwide [1]. Two NS3 protease inhibitors Bocepreir and Telaprevir have been approved as a standard of care for HCV genotype 1 patients and can be used with triple therapy (PEG-IFN- α, ribavirin and Boceprevir or Telaprevir) [9]. There are several HCV NS3 protease inhibitors in development, such as telaprevir (VX-950), boceprevir (SCH- 503034), ITMN-191, TMC435350, MK-7009 and ACH-806 (GS-9132) [17].
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