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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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-11-01
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| Series: | Chemistry Proceedings |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2673-4583/14/1/85 |
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| Summary: | 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. |
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| ISSN: | 2673-4583 |