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Journal Article
Research Support, Non-U.S. Gov't
Novel peptidyl α-aminoalkylphosphonates as inhibitors of hepatitis C virus NS3/4A protease.
Antiviral Research 2017 August
Herein, we describe the synthesis and application of novel phosphonic inhibitors designed to target the NS3/4A protease, which is crucial for the life cycle of hepatitis C virus. We examined the inhibitory potency of our synthesized compounds against two genotypes (1a and 1b) of NS3/4A protease and four mutant strains of HCV. The most potent inhibitors displayed k2 /KI values of 79 850 M-1 s-1 and 60 850 M-1 s-1 against genotype 1a and 1b protease, respectively. Further in vitro evaluation of the most potent inhibitors revealed that vastly reduced HCV replication. Cellular toxicity, plasma stability, reactivity with selected human proteases as well the stability of inhibitor-protease complex and its intracellular availability are also discussed.
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