Tomatidine and Patchouli Alcohol as Inhibitors of SARS-CoV-2 Enzymes (3CLpro, PLpro and NSP15) by Molecular Docking and Molecular Dynamics Simulations
Considering the current dramatic and fatal situation due to the high spreading of SARS-CoV-2 infection, there is an urgent unmet medical need to identify novel and effective approaches for prevention and treatment of Coronavirus disease (COVID 19) by re-evaluating and repurposing of known drugs. For...
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| Format: | Article |
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MDPI AG
2021-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/19/10693 |
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| author | Rafat Zrieq Iqrar Ahmad Mejdi Snoussi Emira Noumi Marcello Iriti Fahad D. Algahtani Harun Patel Mohd Saeed Munazzah Tasleem Shadi Sulaiman Kaïss Aouadi Adel Kadri |
| author_facet | Rafat Zrieq Iqrar Ahmad Mejdi Snoussi Emira Noumi Marcello Iriti Fahad D. Algahtani Harun Patel Mohd Saeed Munazzah Tasleem Shadi Sulaiman Kaïss Aouadi Adel Kadri |
| author_sort | Rafat Zrieq |
| collection | DOAJ |
| description | Considering the current dramatic and fatal situation due to the high spreading of SARS-CoV-2 infection, there is an urgent unmet medical need to identify novel and effective approaches for prevention and treatment of Coronavirus disease (COVID 19) by re-evaluating and repurposing of known drugs. For this, tomatidine and patchouli alcohol have been selected as potential drugs for combating the virus. The hit compounds were subsequently docked into the active site and molecular docking analyses revealed that both drugs can bind the active site of SARS-CoV-2 3CLpro, PLpro, NSP15, COX-2 and PLA2 targets with a number of important binding interactions. To further validate the interactions of promising compound tomatidine, Molecular dynamics study of 100 ns was carried out towards 3CLpro, NSP15 and COX-2. This indicated that the protein-ligand complex was stable throughout the simulation period, and minimal backbone fluctuations have ensued in the system. Post dynamic MM-GBSA analysis of molecular dynamics data showed promising mean binding free energy 47.4633 ± 9.28, 51.8064 ± 8.91 and 54.8918 ± 7.55 kcal/mol, respectively. Likewise, in silico ADMET studies of the selected ligands showed excellent pharmacokinetic properties with good absorption, bioavailability and devoid of toxicity. Therefore, patchouli alcohol and especially, tomatidine may provide prospect treatment options against SARS-CoV-2 infection by potentially inhibiting virus duplication though more research is guaranteed and secured. |
| first_indexed | 2024-03-10T06:58:51Z |
| format | Article |
| id | doaj.art-64f56057593c408ea472210b0a2fef26 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:58:51Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-64f56057593c408ea472210b0a2fef262023-11-22T16:13:56ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122191069310.3390/ijms221910693Tomatidine and Patchouli Alcohol as Inhibitors of SARS-CoV-2 Enzymes (3CLpro, PLpro and NSP15) by Molecular Docking and Molecular Dynamics SimulationsRafat Zrieq0Iqrar Ahmad1Mejdi Snoussi2Emira Noumi3Marcello Iriti4Fahad D. Algahtani5Harun Patel6Mohd Saeed7Munazzah Tasleem8Shadi Sulaiman9Kaïss Aouadi10Adel Kadri11Department of Public Health, College of Public Health and Health Informatics, University of Ha’il, Ha’il 81451, Saudi ArabiaDivision of Computer Aided Drug Design, Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra 425405, IndiaDepartment of Biology, College of Science, University of Ha’il City, P.O. 2440, Ha’il 2440, Saudi ArabiaDepartment of Biology, College of Science, University of Ha’il City, P.O. 2440, Ha’il 2440, Saudi ArabiaDepartment of Agricultural and Environmental Sciences, Università degli Studi di Milano, 20133 Milano, ItalyDepartment of Public Health, College of Public Health and Health Informatics, University of Ha’il, Ha’il 81451, Saudi ArabiaDivision of Computer Aided Drug Design, Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra 425405, IndiaDepartment of Biology, College of Science, University of Ha’il City, P.O. 2440, Ha’il 2440, Saudi ArabiaSchool of Electronic Science and Engineering, University of Electronic Science and Technology of China, Chengdu 610054, ChinaDepartment of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, University of Ha’il, Ha’il 81451, Saudi ArabiaDepartment of Chemistry, College of Science, Qassim University, Buraidah 51452, Saudi ArabiaDepartment of Chemistry, Faculty of Science and Arts of Baljurashi, Albaha University, Al Bahah 65731, Saudi ArabiaConsidering the current dramatic and fatal situation due to the high spreading of SARS-CoV-2 infection, there is an urgent unmet medical need to identify novel and effective approaches for prevention and treatment of Coronavirus disease (COVID 19) by re-evaluating and repurposing of known drugs. For this, tomatidine and patchouli alcohol have been selected as potential drugs for combating the virus. The hit compounds were subsequently docked into the active site and molecular docking analyses revealed that both drugs can bind the active site of SARS-CoV-2 3CLpro, PLpro, NSP15, COX-2 and PLA2 targets with a number of important binding interactions. To further validate the interactions of promising compound tomatidine, Molecular dynamics study of 100 ns was carried out towards 3CLpro, NSP15 and COX-2. This indicated that the protein-ligand complex was stable throughout the simulation period, and minimal backbone fluctuations have ensued in the system. Post dynamic MM-GBSA analysis of molecular dynamics data showed promising mean binding free energy 47.4633 ± 9.28, 51.8064 ± 8.91 and 54.8918 ± 7.55 kcal/mol, respectively. Likewise, in silico ADMET studies of the selected ligands showed excellent pharmacokinetic properties with good absorption, bioavailability and devoid of toxicity. Therefore, patchouli alcohol and especially, tomatidine may provide prospect treatment options against SARS-CoV-2 infection by potentially inhibiting virus duplication though more research is guaranteed and secured.https://www.mdpi.com/1422-0067/22/19/10693tomatidinepatchouli alcoholCOVID-19drug repurposingdocking studydynamic simulation |
| spellingShingle | Rafat Zrieq Iqrar Ahmad Mejdi Snoussi Emira Noumi Marcello Iriti Fahad D. Algahtani Harun Patel Mohd Saeed Munazzah Tasleem Shadi Sulaiman Kaïss Aouadi Adel Kadri Tomatidine and Patchouli Alcohol as Inhibitors of SARS-CoV-2 Enzymes (3CLpro, PLpro and NSP15) by Molecular Docking and Molecular Dynamics Simulations International Journal of Molecular Sciences tomatidine patchouli alcohol COVID-19 drug repurposing docking study dynamic simulation |
| title | Tomatidine and Patchouli Alcohol as Inhibitors of SARS-CoV-2 Enzymes (3CLpro, PLpro and NSP15) by Molecular Docking and Molecular Dynamics Simulations |
| title_full | Tomatidine and Patchouli Alcohol as Inhibitors of SARS-CoV-2 Enzymes (3CLpro, PLpro and NSP15) by Molecular Docking and Molecular Dynamics Simulations |
| title_fullStr | Tomatidine and Patchouli Alcohol as Inhibitors of SARS-CoV-2 Enzymes (3CLpro, PLpro and NSP15) by Molecular Docking and Molecular Dynamics Simulations |
| title_full_unstemmed | Tomatidine and Patchouli Alcohol as Inhibitors of SARS-CoV-2 Enzymes (3CLpro, PLpro and NSP15) by Molecular Docking and Molecular Dynamics Simulations |
| title_short | Tomatidine and Patchouli Alcohol as Inhibitors of SARS-CoV-2 Enzymes (3CLpro, PLpro and NSP15) by Molecular Docking and Molecular Dynamics Simulations |
| title_sort | tomatidine and patchouli alcohol as inhibitors of sars cov 2 enzymes 3clpro plpro and nsp15 by molecular docking and molecular dynamics simulations |
| topic | tomatidine patchouli alcohol COVID-19 drug repurposing docking study dynamic simulation |
| url | https://www.mdpi.com/1422-0067/22/19/10693 |
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