Virtual Screening of Natural Compounds as Potential SARS-CoV-2 Main Protease Inhibitors: A Molecular Docking and Molecular Dynamics Simulation Guided Approach
The 2019 coronavirus (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has significantly impacted human lives, overburdened the healthcare system, and weakened global economies. The lack of specific drugs against SARS-CoV-2 is a significant hurdle toward the...
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2023-11-01
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| author | Deepak K. Lokwani Sangita R. Chavan Aniket P. Sarkate Prabhu M. Natarajan Vidhya R. Umapathy Shirish P. Jain |
| author_facet | Deepak K. Lokwani Sangita R. Chavan Aniket P. Sarkate Prabhu M. Natarajan Vidhya R. Umapathy Shirish P. Jain |
| author_sort | Deepak K. Lokwani |
| collection | DOAJ |
| description | The 2019 coronavirus (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has significantly impacted human lives, overburdened the healthcare system, and weakened global economies. The lack of specific drugs against SARS-CoV-2 is a significant hurdle toward the successful treatment of COVID-19. The SARS-CoV-2 Main protease (M<sup>pro</sup>) is considered an appealing target because of its role in replication in host cells. Plant-derived natural compounds are being largely tested for their efficacy against COVID-19 targets to combat SARS-CoV-2 infection. To discover hit compounds that can be used alone or in combination with repositioned drugs, we curated a set of 224,205 natural product structures from the ZINC database and virtually screened it against COVID-19 M<sup>pro</sup>. Sequential docking protocols involving different levels of exhaustiveness were performed to screen a library of natural compounds. The final 88 compounds were selected and post-processed using the MM-GBSA analysis for the generation of binding free energies. The top four compounds (ZINC000085626103, ZINC000085569275, ZINC000085625768, and ZINC000085488571) showed higher affinity against the COVID-19 M<sup>pro</sup> enzyme selected for MD simulation studies. The RMSD, RMSF, and RoG analysis of all four compound–protein complexes indicated absolute stability during a 100 ns MD run. Furthermore, the post-MD simulation binding free energies were calculated for all four compounds and were found to be in the range of −38.29 to −18.07 kcal/mol. The in silico virtual screening results suggested that the selected natural compounds have the potential to be developed as a COVID-19 M<sup>pro</sup> inhibitor and can be explored further for experimental research to evaluate the in vitro and in vivo efficacy of these compounds for the treatment of COVID-19. |
| format | Article |
| id | doaj-art-8698b6e1869e4073a0e1699bbd3bc730 |
| institution | OA Journals |
| issn | 2673-4583 |
| language | English |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Chemistry Proceedings |
| spelling | doaj-art-8698b6e1869e4073a0e1699bbd3bc7302025-08-20T02:00:35ZengMDPI AGChemistry Proceedings2673-45832023-11-011418510.3390/ecsoc-27-16049Virtual Screening of Natural Compounds as Potential SARS-CoV-2 Main Protease Inhibitors: A Molecular Docking and Molecular Dynamics Simulation Guided ApproachDeepak K. Lokwani0Sangita R. Chavan1Aniket P. Sarkate2Prabhu M. Natarajan3Vidhya R. Umapathy4Shirish P. Jain5Department of Pharmaceutical Chemistry, Rajarshi Shahu College of Pharmacy, Buldhana 443001, IndiaDepartment of Pharmaceutical Chemistry, Rajarshi Shahu College of Pharmacy, Buldhana 443001, IndiaDepartment of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431004, IndiaDepartment of Clinical Sciences, Center of Medical and Bio-Allied Health Sciences and Research, College of Dentistry, Ajman University, Ajman P.O. Box 346, United Arab EmiratesDepartment of Public Health Dentistry, Thai Moogambigai Dental College and Hospital, Chennai 600107, IndiaDepartment of Pharmaceutical Chemistry, Rajarshi Shahu College of Pharmacy, Buldhana 443001, IndiaThe 2019 coronavirus (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has significantly impacted human lives, overburdened the healthcare system, and weakened global economies. The lack of specific drugs against SARS-CoV-2 is a significant hurdle toward the successful treatment of COVID-19. The SARS-CoV-2 Main protease (M<sup>pro</sup>) is considered an appealing target because of its role in replication in host cells. Plant-derived natural compounds are being largely tested for their efficacy against COVID-19 targets to combat SARS-CoV-2 infection. To discover hit compounds that can be used alone or in combination with repositioned drugs, we curated a set of 224,205 natural product structures from the ZINC database and virtually screened it against COVID-19 M<sup>pro</sup>. Sequential docking protocols involving different levels of exhaustiveness were performed to screen a library of natural compounds. The final 88 compounds were selected and post-processed using the MM-GBSA analysis for the generation of binding free energies. The top four compounds (ZINC000085626103, ZINC000085569275, ZINC000085625768, and ZINC000085488571) showed higher affinity against the COVID-19 M<sup>pro</sup> enzyme selected for MD simulation studies. The RMSD, RMSF, and RoG analysis of all four compound–protein complexes indicated absolute stability during a 100 ns MD run. Furthermore, the post-MD simulation binding free energies were calculated for all four compounds and were found to be in the range of −38.29 to −18.07 kcal/mol. The in silico virtual screening results suggested that the selected natural compounds have the potential to be developed as a COVID-19 M<sup>pro</sup> inhibitor and can be explored further for experimental research to evaluate the in vitro and in vivo efficacy of these compounds for the treatment of COVID-19.https://www.mdpi.com/2673-4583/14/1/85COVID-19 M<sup>pro</sup> inhibitorZINC databasedockingMD simulationsMM-GBSA |
| spellingShingle | Deepak K. Lokwani Sangita R. Chavan Aniket P. Sarkate Prabhu M. Natarajan Vidhya R. Umapathy Shirish P. Jain Virtual Screening of Natural Compounds as Potential SARS-CoV-2 Main Protease Inhibitors: A Molecular Docking and Molecular Dynamics Simulation Guided Approach Chemistry Proceedings COVID-19 M<sup>pro</sup> inhibitor ZINC database docking MD simulations MM-GBSA |
| title | Virtual Screening of Natural Compounds as Potential SARS-CoV-2 Main Protease Inhibitors: A Molecular Docking and Molecular Dynamics Simulation Guided Approach |
| title_full | Virtual Screening of Natural Compounds as Potential SARS-CoV-2 Main Protease Inhibitors: A Molecular Docking and Molecular Dynamics Simulation Guided Approach |
| title_fullStr | Virtual Screening of Natural Compounds as Potential SARS-CoV-2 Main Protease Inhibitors: A Molecular Docking and Molecular Dynamics Simulation Guided Approach |
| title_full_unstemmed | Virtual Screening of Natural Compounds as Potential SARS-CoV-2 Main Protease Inhibitors: A Molecular Docking and Molecular Dynamics Simulation Guided Approach |
| title_short | Virtual Screening of Natural Compounds as Potential SARS-CoV-2 Main Protease Inhibitors: A Molecular Docking and Molecular Dynamics Simulation Guided Approach |
| title_sort | virtual screening of natural compounds as potential sars cov 2 main protease inhibitors a molecular docking and molecular dynamics simulation guided approach |
| topic | COVID-19 M<sup>pro</sup> inhibitor ZINC database docking MD simulations MM-GBSA |
| url | https://www.mdpi.com/2673-4583/14/1/85 |
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