In Silico Identification of Some Novel Ketoamides as Potential Pan-Genotypic HCV NS3/4A Protease Inhibitors with Drug-Likeness, Pharmacokinetic ADME Profiles and Synthetic Accessibility Predictions
نویسندگان
1 Department of Chemistry, Faculty of Physical Science, Ahmadu Bello University, P.M.B. 1044, Zaria, Kaduna State, Nigeria
2 Department of Chemistry, Faculty of Physical Science, Ahmadu Bello University, P.M.B. 1044, Zaria, Kaduna State, Nigeria
3 Department of Chemistry, Faculty of Physical Science, Ahmadu Bello University, P.M.B. 1044, Zaria, Kaduna State, Nigeria
4 Department of Chemistry, Faculty of Physical Science, Ahmadu Bello University, P.M.B. 1044, Zaria, Kaduna State, Nigeria
5 Department of Chemistry, Faculty of Physical Science, Ahmadu Bello University, P.M.B. 1044, Zaria, Kaduna State, Nigeria
doi
10.22034/ajca.2022.329332.1302چکیده
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 NS3/A4 enzyme plays a critical role in the HCV entire lifespan and proliferation. Consequently, inhibitors of the HCV NS3/A4 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 NS3/A4 enzyme inhibitors to find a novel potential drug as a lead candidate. To Voxilaprevir as a reference medicine, our findings revealed that three HCV NS3/A4 protease inhibitors (Pubchem CID: 44158040, 44158107, and 11479303) were identified as the best drugs for blocking hepatitis C virus NS3/A4 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 NS3/A4 inhibitors in order to find new and improved HCV antiviral drugs.
