Computer-Aided Design of Thiazolone Derivatives Targeting HCV NS5B Allosteric Site Using Molecular Docking, ADME/Tox Profiling, and Dynamics
International Pharmacy Acta,
Vol. 8 No. 1 (2025),
6 April 2025
,
Page e10: 1-8
https://doi.org/10.22037/ipa.v8i1.50712
Abstract
Hepatitis C virus (HCV) remains a major health concern, with the NS5B RNA-dependent RNA polymerase representing a crucial target for antiviral drug discovery. This study aimed to identify selective NS5B inhibitors from a library of thiazolone derivatives using an integrated computer-aided drug design workflow. Molecular docking was performed with AutoDock Vina via PyRx on 1000 compounds, and pharmacokinetic and toxicity properties were evaluated using SwissADME and PreADMET. Normal Mode Analysis (NMA) was then applied through the iMODS server to assess the dynamic effects of ligand binding on protein flexibility. Three compounds, CID137131214, CID135435208, and CID2329878, demonstrated strong binding affinities, favorable ADME/Tox profiles, and key interactions with the NS5B allosteric site. Notably, CID135435208 induced a rigidifying effect, supporting its inhibitory potential. These results highlight promising scaffolds for further biological validation and provide a rational framework for the design of novel HCV therapeutics. However, this study is limited by the lack of experimental validation, which will be addressed in future work.
- HCV
- NS5B polymerase
- thiazolone derivatives
- molecular docking
- ADME/Tox
- normal mode analysis
How to Cite
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