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
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 discov...
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| Format: | Article |
| Language: | English |
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Public Library of Science
2024
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| Online Access: | http://umpir.ump.edu.my/id/eprint/40860/1/Phenolic%20compounds%20of%20Theobroma%20cacao%20L.%20show%20potential%20against%20dengue.pdf |
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| author | Moyeenul Huq, A. K. M. Roney, Miah Dubey, Amit Muhammad Hassan, Nasir Tufail, Aisha Mohd Fadhlizil Fasihi, Mohd Aluwi Wan Maznah, Wan Ishak Islam, Md. Rabiul Saiful Nizam, Tajuddin |
| author_facet | Moyeenul Huq, A. K. M. Roney, Miah Dubey, Amit Muhammad Hassan, Nasir Tufail, Aisha Mohd Fadhlizil Fasihi, Mohd Aluwi Wan Maznah, Wan Ishak Islam, Md. Rabiul Saiful Nizam, Tajuddin |
| author_sort | Moyeenul Huq, A. K. M. |
| collection | UMP |
| description | 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. |
| first_indexed | 2024-04-09T03:52:30Z |
| format | Article |
| id | UMPir40860 |
| institution | Universiti Malaysia Pahang |
| language | English |
| last_indexed | 2024-09-25T03:48:31Z |
| publishDate | 2024 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | UMPir408602024-06-26T03:34:50Z http://umpir.ump.edu.my/id/eprint/40860/ 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 Moyeenul Huq, A. K. M. Roney, Miah Dubey, Amit Muhammad Hassan, Nasir Tufail, Aisha Mohd Fadhlizil Fasihi, Mohd Aluwi Wan Maznah, Wan Ishak Islam, Md. Rabiul Saiful Nizam, Tajuddin Q Science (General) TP Chemical technology 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. Public Library of Science 2024-03 Article PeerReviewed pdf en cc_by_4 http://umpir.ump.edu.my/id/eprint/40860/1/Phenolic%20compounds%20of%20Theobroma%20cacao%20L.%20show%20potential%20against%20dengue.pdf 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) https://doi.org/10.1371/journal.pone.0299238 10.1371/journal.pone.0299238 |
| spellingShingle | Q Science (General) TP Chemical technology Moyeenul Huq, A. K. M. Roney, Miah Dubey, Amit Muhammad Hassan, Nasir Tufail, Aisha Mohd Fadhlizil Fasihi, Mohd Aluwi Wan Maznah, Wan Ishak Islam, Md. Rabiul Saiful Nizam, Tajuddin 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 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Q Science (General) TP Chemical technology |
| url | http://umpir.ump.edu.my/id/eprint/40860/1/Phenolic%20compounds%20of%20Theobroma%20cacao%20L.%20show%20potential%20against%20dengue.pdf |
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