In Silico Identification of Some Novel Ketoamides as Potential Pan-Genotypic HCV NS۳/۴A Protease Inhibitors with Drug-Likeness, Pharmacokinetic ADME Profiles and Synthetic Accessibility Predictions

Hepatitis C virus (HCV) infection promotes death rates worldwide. As a result, there is a constant need to improve current HCV therapy and produce new drugs. The NS۳/A۴ enzyme plays a critical role in the HCV entire lifespan and proliferation. Consequently, inhibitors of the HCV NS۳/A۴ enzyme are a great spot to start exploring new drug candidates. In this study, the high throughput in silico screening of the Pubchem database was used to analyze a set of ketoamides as HCV NS۳/A۴ enzyme inhibitors to find a novel potential drug as a lead candidate. To Voxilaprevir as a reference medicine, our findings revealed that three HCV NS۳/A۴ protease inhibitors (Pubchem CID: ۴۴۱۵۸۰۴۰, ۴۴۱۵۸۱۰۷, and ۱۱۴۷۹۳۰۳) were identified as the best drugs for blocking hepatitis C virus NS۳/A۴ protease. The QSAR was performed to study the relationships between the structural features of the targets and their binding affinity by developing statistical models. The reported compounds had a higher binding affinity for the target receptor than Voxilaprevir, the reference drug. This study could be important in understanding the physicochemical and binding affinity of HCV NS۳/A۴ inhibitors in order to find new and improved HCV antiviral drugs.

Keywords:

Structure-based design , HCV NS۳/A۴ protease , Drug-likeness , In silico approach