Lim, See Khai and Othman, Rozana and Yusof, Rohana and Heh, Choon Han (2021) Rational drug discovery: Ellagic acid as a potent dual-target inhibitor against hepatitis C virus genotype 3 (HCV G3) NS3 enzymes. Chemical Biology & Drug Design, 97 (1). pp. 28-40. ISSN 1747-0277, DOI https://doi.org/10.1111/cbdd.13756.
Full text not available from this repository.Abstract
Structure-based virtual screening (SBVS) has served as a popular strategy for rational drug discovery. In this study, we aimed to discover novel benzopyran-based inhibitors that targeted the NS3 enzymes (NS3/4A protease and NS3 helicase) of HCV G3 using a combination of in silico and in vitro approaches. With the aid of SBVS, six novel compounds were discovered to inhibit HCV G3 NS3/4A protease and two phytochemicals (ellagic acid and myricetin) were identified as dual-target inhibitors that inhibited both NS3/4A protease and NS3 helicase in vitro (IC50 = 40.37 +/- 5.47 nmand 6.58 +/- 0.99 mu m, respectively). Inhibitory activities against the replication of HCV G3 replicons were further assessed in a cell-based system with four compounds showed dose-dependent inhibition. Compound P8 was determined to be the most potent compound from the cell-based assay with an EC(50)of 19.05 mu m. The dual-target inhibitor, ellagic acid, was determined as the second most potent (EC50 = 32.37 mu m) and the most selective in its inhibitory activity against the replication of HCV replicons, without severely affecting the viability of the host cells (selectivity index > 6.18).
| Item Type: | Article |
|---|---|
| Funders: | Universiti Malaya (BKS065-2017), Universiti Malaya (PG076-2016A) |
| Uncontrolled Keywords: | Benzopyran; Ellagic acid; Helicase; Hepatitis C virus; NS3; 4A protease; Virtual screening |
| Subjects: | R Medicine > RM Therapeutics. Pharmacology |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 05 Apr 2022 07:43 |
| Last Modified: | 05 Apr 2022 07:43 |
| URI: | http://eprints.um.edu.my/id/eprint/26655 |
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