Sakhor, W. and Teoh, T. C. and Yusof, R. and Lim, S. K. and Razif, M. F. M. (2020) Discovery of small molecule inhibitors against the NS3/4A serine protease of Hepatitis C virus genotype 3 via high-throughput virtual screening and in vitro evaluations. Tropical Biomedicine, 37 (3). pp. 609-625. ISSN 0127-5720,
Full text not available from this repository.Abstract
The hepatitis C virus (HCV) consists of eight genotypes and 90 subtypes, with genotype (GT) 3 being the second most common globally and is linked to higher incidences of steatosis and rapid development of fibrosis and cirrhosis. The NS3/4A serine protease, a heterodimer complex of two HCV non-structural proteins, is an effective target for pharmaceutical intervention due to its essential roles in processing HCV polyproteins and inhibiting innate immunity. This study combines structure-based virtual screening (SBVS) of predefined compound libraries, pharmacokinetic prediction (ADME/T) and in vitro evaluation to identify potential low molecular weight (<500 Dalton) inhibitors of the NS3/4A serine protease (GT3). In silico screening of ZINC and PubChem libraries yielded five selected compounds as potential candidates. Dose-dependent inhibition of the NS3/4A serine protease and HCV replication in HuH-7.5 cells revealed that compound A (PubChem ID No. 16672637) exhibited inhibition towards HCV GT3 with an IC50 of 106.7 mu M and BC EC50 of 25.8 mu M, respectively. Thus, compound A may be developed as a potent, low molecular weight drug against the HCV NS3/4A serine protease of GT3.
| Item Type: | Article |
|---|---|
| Funders: | Ministry of Education Malaysia-Transdisciplinary Research Grants Scheme [Grant No: TR001B-2014B], Universiti Malaya [Grant No: PG238-2016A] |
| Uncontrolled Keywords: | Antiviral Agents; Cell Line; Drug Evaluation, Preclinical; Hepacivirus; Humans; Molecular Docking Simulation; Molecular Structure; Protease Inhibitors; Protein Structure, Tertiary; Serine Proteases; Viral Nonstructural Proteins |
| Subjects: | Q Science > QH Natural history > QH301 Biology R Medicine > R Medicine (General) R Medicine > RS Pharmacy and materia medica |
| Divisions: | Faculty of Medicine > Department of Molecular Medicine Faculty of Science > Institute of Biological Sciences Faculty of Pharmacy > Department of Pharmaceutical Chemistry |
| Depositing User: | Ms Zaharah Ramly |
| Date Deposited: | 28 Oct 2024 07:38 |
| Last Modified: | 28 Oct 2024 07:38 |
| URI: | http://eprints.um.edu.my/id/eprint/36458 |
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