Computer-assisted drug repurposing for thymidylate kinase drug target in monkeypox virus
IntroductionMonkeypox is a zoonotic disease caused by brick-shaped enveloped monkeypox (Mpox) virus that belongs to the family of ancient viruses known as Poxviridae. Subsequently, the viruses have been reported in various countries. The virus is transmitted by respiratory droplets, skin lesions, an...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2023.1159389/full |
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| author | Amar Ajmal Arif Mahmood Chandni Hayat Mohammed Ageeli Hakami Bader S. Alotaibi Muhammad Umair Ashraf N. Abdalla Ping Li Pei He Abdul Wadood Junjian Hu |
| author_facet | Amar Ajmal Arif Mahmood Chandni Hayat Mohammed Ageeli Hakami Bader S. Alotaibi Muhammad Umair Ashraf N. Abdalla Ping Li Pei He Abdul Wadood Junjian Hu |
| author_sort | Amar Ajmal |
| collection | DOAJ |
| description | IntroductionMonkeypox is a zoonotic disease caused by brick-shaped enveloped monkeypox (Mpox) virus that belongs to the family of ancient viruses known as Poxviridae. Subsequently, the viruses have been reported in various countries. The virus is transmitted by respiratory droplets, skin lesions, and infected body fluids. The infected patients experience fluid-filled blisters, maculopapular rash, myalgia, and fever. Due to the lack of effective drugs or vaccines, there is a need to identify the most potent and effective drugs to reduce the spread of monkeypox. The current study aimed to use computational methods to quickly identify potentially effective drugs against the Mpox virus.MethodsIn our study, the Mpox protein thymidylate kinase (A48R) was targeted because it is a unique drug target. We screened a library of 9000 FDA-approved compounds of the DrugBank database by using various in silico approaches, such as molecular docking and molecular dynamic (MD) simulation.ResultsBased on docking score and interaction analysis, compounds DB12380, DB13276, DB13276, DB11740, DB14675, DB11978, DB08526, DB06573, DB15796, DB08223, DB11736, DB16250, and DB16335 were predicted as the most potent. To examine the dynamic behavior and stability of the docked complexes, three compounds—DB16335, DB15796, and DB16250 —along with the Apo state were simulated for 300ns. The results revealed that compound DB16335 revealed the best docking score (-9.57 kcal/mol) against the Mpox protein thymidylate kinase.DiscussionAdditionally, during the 300 ns MD simulation period, thymidylate kinase DB16335 showed great stability. Further, in vitro and in vivo study is recommended for the final predicted compounds. |
| first_indexed | 2024-03-13T08:54:12Z |
| format | Article |
| id | doaj.art-4aee326ba67349619a11bd43f7735bbc |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-03-13T08:54:12Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-4aee326ba67349619a11bd43f7735bbc2023-05-29T04:19:30ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882023-05-011310.3389/fcimb.2023.11593891159389Computer-assisted drug repurposing for thymidylate kinase drug target in monkeypox virusAmar Ajmal0Arif Mahmood1Chandni Hayat2Mohammed Ageeli Hakami3Bader S. Alotaibi4Muhammad Umair5Ashraf N. Abdalla6Ping Li7Pei He8Abdul Wadood9Junjian Hu10Department of Biochemistry, Computational Medicinal Chemistry Laboratory, Abdul Wali Khan University, Mardan, PakistanCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, ChinaDepartment of Biochemistry, Computational Medicinal Chemistry Laboratory, Abdul Wali Khan University, Mardan, PakistanDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Al-Quwayiyah, Shaqra University, Riyadh, Saudi ArabiaDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Al-Quwayiyah, Shaqra University, Riyadh, Saudi ArabiaDepartment of Life Sciences, School of Science, University of Management and Technology (UMT), Lahore, PakistanDepartment of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi ArabiaInstitute of Biomedical Sciences, Shanxi University, Taiyuan, ChinaDepartment of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Biochemistry, Computational Medicinal Chemistry Laboratory, Abdul Wali Khan University, Mardan, PakistanDepartment of Central Laboratory, SSL Central Hospital of Dongguan City, Affiliated Dongguan Shilong People’s Hospital of Southern Medical University, Dongguan, ChinaIntroductionMonkeypox is a zoonotic disease caused by brick-shaped enveloped monkeypox (Mpox) virus that belongs to the family of ancient viruses known as Poxviridae. Subsequently, the viruses have been reported in various countries. The virus is transmitted by respiratory droplets, skin lesions, and infected body fluids. The infected patients experience fluid-filled blisters, maculopapular rash, myalgia, and fever. Due to the lack of effective drugs or vaccines, there is a need to identify the most potent and effective drugs to reduce the spread of monkeypox. The current study aimed to use computational methods to quickly identify potentially effective drugs against the Mpox virus.MethodsIn our study, the Mpox protein thymidylate kinase (A48R) was targeted because it is a unique drug target. We screened a library of 9000 FDA-approved compounds of the DrugBank database by using various in silico approaches, such as molecular docking and molecular dynamic (MD) simulation.ResultsBased on docking score and interaction analysis, compounds DB12380, DB13276, DB13276, DB11740, DB14675, DB11978, DB08526, DB06573, DB15796, DB08223, DB11736, DB16250, and DB16335 were predicted as the most potent. To examine the dynamic behavior and stability of the docked complexes, three compounds—DB16335, DB15796, and DB16250 —along with the Apo state were simulated for 300ns. The results revealed that compound DB16335 revealed the best docking score (-9.57 kcal/mol) against the Mpox protein thymidylate kinase.DiscussionAdditionally, during the 300 ns MD simulation period, thymidylate kinase DB16335 showed great stability. Further, in vitro and in vivo study is recommended for the final predicted compounds.https://www.frontiersin.org/articles/10.3389/fcimb.2023.1159389/fullmonkeypoxhomology modelingmolecular dockingMD simulationdrugs development |
| spellingShingle | Amar Ajmal Arif Mahmood Chandni Hayat Mohammed Ageeli Hakami Bader S. Alotaibi Muhammad Umair Ashraf N. Abdalla Ping Li Pei He Abdul Wadood Junjian Hu Computer-assisted drug repurposing for thymidylate kinase drug target in monkeypox virus Frontiers in Cellular and Infection Microbiology monkeypox homology modeling molecular docking MD simulation drugs development |
| title | Computer-assisted drug repurposing for thymidylate kinase drug target in monkeypox virus |
| title_full | Computer-assisted drug repurposing for thymidylate kinase drug target in monkeypox virus |
| title_fullStr | Computer-assisted drug repurposing for thymidylate kinase drug target in monkeypox virus |
| title_full_unstemmed | Computer-assisted drug repurposing for thymidylate kinase drug target in monkeypox virus |
| title_short | Computer-assisted drug repurposing for thymidylate kinase drug target in monkeypox virus |
| title_sort | computer assisted drug repurposing for thymidylate kinase drug target in monkeypox virus |
| topic | monkeypox homology modeling molecular docking MD simulation drugs development |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2023.1159389/full |
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