| الوصف: |
Global urbanization and the growing geographic range of Aedes mosquitoes are the leading causes of the increase in Chikungunya infections, and the lack of a particular antiviral therapy for the disease is a cause of great concern. This article represents the research done so far to find small compounds, like natural drug candidates, that could block the activity of envelope glycoprotein and work as an antiviral to treat CHIKV infection. Here, we used a wide range of in-silico drug design techniques, including molecular docking, molecular dynamics simulation, ADME/toxicity, post-docking MM-GBSA, PCA, and DCCM, to discover potential drug candidates targeting the specific protein of interest. Out of 483 natural compounds, 180 compounds passed the ADMET analysis, and the molecular docking identified the top three lead candidates (CID: 439533, CID: 3082330, and CID: 471) with an effective binding affinity of −4.686, −4.663, and −4.594 (kcal/mol), respectively. Both the control ligand and the lead compounds interacted with the common amino acid residues (TYR301, ILE231, PHE164, ILE321, GLN113), which indicates that lead compounds and the control ligand both bind in the common active site of the protein. Negative binding free energy of CID: 439533, CID: 3082330, CID: 471 were −35.07, −34.89, and −32.5 kcal/mol, respectively. These molecules were then further assessed using MD simulation, which verified the molecules!ˋ stability and binding to the targeted protein. The stability of the protein-ligand docking complex structure was evaluated using MD simulation. The ligands assessed in this study, CID: 439533, CID: 3082330, and CID: 471, unveiled the significant stability of the proteins' binding site in the MD simulation study, which also showed a high negative binding free energy value. Three principal components (PC1, PC2, PC3) for the lead compound CID: 3082330 (2′,3,5,7-Tetrahydroxyflavanone) were (50.08%), (22.61%), and (4.41%), respectively, which we can suggest as the best drug candidate, followed by CID: 439533. Both compounds may potentially inhibit CHIKV envelope glycoprotein activity. |
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