Synthesis and Kinetic Analysis of HCV NS3/4a Protease InhibitorsPublic
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Hepatitis C virus (HCV) is the leading cause of chronic liver disease in the world. To make more effective antiviral therapies, companies started to develop direct acting antiviral drugs that could target specific components of the virus. One target is the NS3/4a protease and while inhibitors (PIs) have been developed, but are susceptible to drug-resistant mutations. The goal of the project was to develop new PIs based on the drug MK-5172 and test inhibition on both wild type and mutant proteases. Three inhibitors were made and analyzed with inhibition assays against both the wt protease and D168A, a mutant. No inhibitor was found to be more potent than MK-5172, however one (WK-27) was found to have very similar Ki values and further study of it could lead to more refined drug design.
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