Moyeenul Huq, A. K. M. and Roney, Miah and Dubey, Amit and Muhammad Hassan, Nasir and Tufail, Aisha and Mohd Fadhlizil Fasihi, Mohd Aluwi and Wan Maznah, Wan Ishak and Islam, Md. Rabiul and Saiful Nizam, Tajuddin (2024) Phenolic compounds of Theobroma cacao L. show potential against dengue RdRp protease enzyme inhibition by In-silico docking, DFT study, MD simulation and MMGBSA calculation. PLoS ONE, 19 (3). pp. 1-20. ISSN 1932-6203. (Published)
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Abstract
Background: Currently, there is no antiviral medication for dengue, a potentially fatal tropical infectious illness spread by two mosquito species, Aedes aegypti and Aedes albopictus. The RdRp protease of dengue virus is a potential therapeutic target. This study focused on the in silico drug discovery of RdRp protease inhibitors. Methods; To assess the potential inhibitory activity of 29 phenolic acids from Theobroma cacao L. against DENV3-NS5 RdRp, a range of computational methods were employed. These included docking, drug-likeness analysis, ADMET prediction, density functional theory (DFT) calculations, and molecular dynamics (MD) simulations. The aim of these studies was to confirm the stability of the ligand-protein complex and the binding pose identified during the docking experiment. Results: Twenty-one compounds were found to have possible inhibitory activities against DENV according to the docking data, and they had a binding affinity of ≥-37.417 kcal/mol for DENV3- enzyme as compared to the reference compound panduratin A. Additionally, the drug-likeness investigation produced four hit compounds that were subjected to ADMET screening to obtain the lead compound, catechin. Based on ELUMO, EHOMO, and band energy gap, the DFT calculations showed strong electronegetivity, favouravle global softness and chemical reactivity with considerable intra-molecular charge transfer between electron-donor to electron-acceptor groups for catechin. The MD simulation result also demonstrated favourable RMSD, RMSF, SASA and H-bonds in at the binding pocket of DENV3-NS5 RdRp for catechin as compared to panduratin A. Conclusion: According to the present findings, catechin showed high binding affinity and sufficient drug-like properties with the appropriate ADMET profiles. Moreover, DFT and MD studies further supported the drug-like action of catechin as a potential therapeutic candidate. Therefore, further in vitro and in vivo research on cocoa and its phytochemical catechin should be taken into consideration to develop as a potential DENV inhibitor.
| Item Type: | Article |
|---|---|
| Additional Information: | Indexed by Scopus |
| Uncontrolled Keywords: | Aedes; Aedes albopictus; Animals; Cacao; Catechin; Chalcones; Dengue; Endopeptidases |
| Subjects: | Q Science > Q Science (General) T Technology > TP Chemical technology |
| Faculty/Division: | Faculty of Industrial Sciences And Technology Institute of Postgraduate Studies Centre for Bioaromatic Research (Bioaromatic Centre) Faculty of Chemical and Process Engineering Technology |
| Depositing User: | Mrs Norsaini Abdul Samat |
| Date Deposited: | 03 Apr 2024 04:29 |
| Last Modified: | 03 Apr 2024 04:29 |
| URI: | http://umpir.ump.edu.my/id/eprint/40860 |
| Download Statistic: | View Download Statistics |
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