Document Type : Research Paper
Authors
1
Department of Biophysics, Faculty of Biological Sciences, Gorgan Branch, Islamic Azad University, Gorgan, Iran
2
Medicinal Plants Research Center, Gorgan Branch, Islamic Azad University, Gorgan, Iran
3
Department of Biophysics, Faculty of Biological Science, Varamin-Pishva Branch, Islamic Azad University, Varamin, I.R. Iran
4
Department of Physics, Varamin-Pishva Branch, Islamic Azad University, Varamin, I.R Iran
5
Department of Biology, Faculty of Science, Gorgan Branch, Islamic Azad University, Gorgan, Iran
Abstract
SARS-CoV-2 is one of the most important novel coronaviruses and was recognized as a major global concern due to the declaration of the pandemic in March 2020. Researchers have attempted to develop antiviral agents against coronavirus, and the Mpro protein may be an effective drug target. To identify potential hit molecules for clinical use, we analyzed the inhibitory effects of phytochemical compounds from ginger and kundur and seven FDA-approved drugs against Mpro. Employing molecular docking and scoring functions, three top phytochemical compounds, gingerone A, astelbin, and L-(-)-catechin, and three reported antiviral drugs, chloroquine, ritonavir, and remdesivir, showed higher interaction profiles. According to the toxicity and ADME properties, L-(−)-catechin and remdesivir were selected for further analysis via MD simulations. The MD results supported by standard analysis (e.g., RMSD, RMSF, Rg, and SASA) revealed that L-(-)-catechin had a greater impact on the Mpro structure than remdesivir. Proteinligand energy calculations via the MM/PBSA method also supported the molecular docking data. Interestingly, our docking studies revealed that L-(-)-catechin has different interactions with Cys145 and His41, which may disrupt the formation of the Cys-His dyad, which is crucial for Mpro protease activity. We believe that due to the significant effect of L-(−)-catechin on the Mpro protein, this compound can be evaluated as a candidate molecule in drug development studies against SARS-CoV-2.
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