Unveiling the antiviral activity of 2′,3,5,7-Tetrahydroxyflavanone as potential inhibitor of chikungunya virus envelope glycoprotein
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 compou...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-01-01
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| Series: | Informatics in Medicine Unlocked |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S235291482400042X |
| _version_ | 1797221769308798976 |
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| author | Noimul Hasan Siddiquee Salina Malek Afsan Ara Tanni Israt Jahan Mitu Sanjida Hossain Arpa Md Rakibul Hasan Sayeda Eshmita Jahan Shammi Cotton Chakma Mahinur Mahinur Shah Wajed Md Ifteker Hossain Md Aktaruzzaman Otun Saha |
| author_facet | Noimul Hasan Siddiquee Salina Malek Afsan Ara Tanni Israt Jahan Mitu Sanjida Hossain Arpa Md Rakibul Hasan Sayeda Eshmita Jahan Shammi Cotton Chakma Mahinur Mahinur Shah Wajed Md Ifteker Hossain Md Aktaruzzaman Otun Saha |
| author_sort | Noimul Hasan Siddiquee |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T13:10:42Z |
| format | Article |
| id | doaj.art-7a0c1928884b4e7794959d2522baf7c8 |
| institution | Directory Open Access Journal |
| issn | 2352-9148 |
| language | English |
| last_indexed | 2024-04-24T13:10:42Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Informatics in Medicine Unlocked |
| spelling | doaj.art-7a0c1928884b4e7794959d2522baf7c82024-04-05T04:41:00ZengElsevierInformatics in Medicine Unlocked2352-91482024-01-0147101486Unveiling the antiviral activity of 2′,3,5,7-Tetrahydroxyflavanone as potential inhibitor of chikungunya virus envelope glycoproteinNoimul Hasan Siddiquee0Salina Malek1Afsan Ara Tanni2Israt Jahan Mitu3Sanjida Hossain Arpa4Md Rakibul Hasan5Sayeda Eshmita Jahan Shammi6Cotton Chakma7Mahinur Mahinur8Shah Wajed9Md Ifteker Hossain10Md Aktaruzzaman11Otun Saha12Department of Microbiology, Noakhali Science and Technology University, Noakhali, 3814, BangladeshDepartment of Biotechnology and Genetic Engineering, Jahangirnagar University, Savar, Dhaka, 1342, BangladeshDepartment of Microbiology, Primeasia University, Dhaka 1213, BangladeshDepartment of Microbiology, Noakhali Science and Technology University, Noakhali, 3814, BangladeshDepartment of Microbiology, Noakhali Science and Technology University, Noakhali, 3814, BangladeshDepartment of Microbiology, Noakhali Science and Technology University, Noakhali, 3814, BangladeshDepartment of Microbiology, Noakhali Science and Technology University, Noakhali, 3814, BangladeshDepartment of Microbiology, Noakhali Science and Technology University, Noakhali, 3814, BangladeshDepartment of Microbiology, Noakhali Science and Technology University, Noakhali, 3814, BangladeshDepartment of Microbiology, Noakhali Science and Technology University, Noakhali, 3814, BangladeshDepartment of Microbiology, Noakhali Science and Technology University, Noakhali, 3814, BangladeshDepartment of Pharmacy, Jashore University of Science and Technology, Jashore, 7408, BangladeshDepartment of Microbiology, Noakhali Science and Technology University, Noakhali, 3814, Bangladesh; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S235291482400042XIn-silico drug designChikungunya virus envelope glycoproteinADMETMolecular docking and post docking MM-GBSAMD simulationPCA |
| spellingShingle | Noimul Hasan Siddiquee Salina Malek Afsan Ara Tanni Israt Jahan Mitu Sanjida Hossain Arpa Md Rakibul Hasan Sayeda Eshmita Jahan Shammi Cotton Chakma Mahinur Mahinur Shah Wajed Md Ifteker Hossain Md Aktaruzzaman Otun Saha Unveiling the antiviral activity of 2′,3,5,7-Tetrahydroxyflavanone as potential inhibitor of chikungunya virus envelope glycoprotein Informatics in Medicine Unlocked In-silico drug design Chikungunya virus envelope glycoprotein ADMET Molecular docking and post docking MM-GBSA MD simulation PCA |
| title | Unveiling the antiviral activity of 2′,3,5,7-Tetrahydroxyflavanone as potential inhibitor of chikungunya virus envelope glycoprotein |
| title_full | Unveiling the antiviral activity of 2′,3,5,7-Tetrahydroxyflavanone as potential inhibitor of chikungunya virus envelope glycoprotein |
| title_fullStr | Unveiling the antiviral activity of 2′,3,5,7-Tetrahydroxyflavanone as potential inhibitor of chikungunya virus envelope glycoprotein |
| title_full_unstemmed | Unveiling the antiviral activity of 2′,3,5,7-Tetrahydroxyflavanone as potential inhibitor of chikungunya virus envelope glycoprotein |
| title_short | Unveiling the antiviral activity of 2′,3,5,7-Tetrahydroxyflavanone as potential inhibitor of chikungunya virus envelope glycoprotein |
| title_sort | unveiling the antiviral activity of 2 3 5 7 tetrahydroxyflavanone as potential inhibitor of chikungunya virus envelope glycoprotein |
| topic | In-silico drug design Chikungunya virus envelope glycoprotein ADMET Molecular docking and post docking MM-GBSA MD simulation PCA |
| url | http://www.sciencedirect.com/science/article/pii/S235291482400042X |
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