학술논문
In silico Screening of Potential SARS-CoV-2 Main Protease Inhibitors from Thymus schimperi
ORIGINAL RESEARCH
ORIGINAL RESEARCH
Document Type
Report
Source
Advances and Applications in Bioinformatics and Chemistry. January 31, 2023, Vol. 16, p1, 13 p.
Subject
Language
English
ISSN
1178-6949
Abstract
Introduction Coronavirus disease 19 (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since its emergence in December 2019, it exerts a big economic and social [...]
Background: COVID-19 is still instigating significant social and economic chaos worldwide; however, there is no approved antiviral drug yet. Here, we used in silico analysis to screen potential SARS-CoV-2 main protease ([M.sup.pro]) inhibitors extracted from the essential oil of Thymus schimperi which could contribute to the discovery of potent anti-SARS-CoV-2 phytochemicals. Methods: The absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles of compounds were determined through SwissADME and ProToxII servers. AutoDock tools were used for molecular docking analysis studies, while Chimera, DS studio, and LigPlot were used for post-docking studies. Molecular dynamic simulations were performed for 200 ns under constant pressure. Results: All compounds exhibited a bioavailability score of [greater than or equal to] 0.55 entailing that at least 55% of the drugs can be absorbed unchanged. Only five (9%), nine (16%) and two (3.6%) of the compounds showed active hepatotoxicity, carcinogenicity, and immunotoxicity, respectively. Except for flourazophore P, which showed a little mutagenicity, all other compounds did not show mutagenic properties. On the other hand, only pinene beta was found to have a little cytotoxicity. Five compounds demonstrated effective binding to the catalytic dyad of the SARS-CoV-2 [M.sup.pro] substrate binding pocket, while two of them (geranylisobutanoate and 3- octane) are found to be the best hits that formed hydrogen bonds with [Glu.sup.166] and [Ser.sup.144] of SARS-CoV-2 [M.sup.pro]. Conclusion: Based on our in silico analysis, top hits from Thymus schimperi may serve as potential anti-SARS-CoV-2 compounds. Further in vitro and in vivo studies are recommended to characterize these compounds for clinical applications. Keywords: structural analysis, SARS-CoV-2, main protease, inhibitors, Thymus schimperi
Background: COVID-19 is still instigating significant social and economic chaos worldwide; however, there is no approved antiviral drug yet. Here, we used in silico analysis to screen potential SARS-CoV-2 main protease ([M.sup.pro]) inhibitors extracted from the essential oil of Thymus schimperi which could contribute to the discovery of potent anti-SARS-CoV-2 phytochemicals. Methods: The absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles of compounds were determined through SwissADME and ProToxII servers. AutoDock tools were used for molecular docking analysis studies, while Chimera, DS studio, and LigPlot were used for post-docking studies. Molecular dynamic simulations were performed for 200 ns under constant pressure. Results: All compounds exhibited a bioavailability score of [greater than or equal to] 0.55 entailing that at least 55% of the drugs can be absorbed unchanged. Only five (9%), nine (16%) and two (3.6%) of the compounds showed active hepatotoxicity, carcinogenicity, and immunotoxicity, respectively. Except for flourazophore P, which showed a little mutagenicity, all other compounds did not show mutagenic properties. On the other hand, only pinene beta was found to have a little cytotoxicity. Five compounds demonstrated effective binding to the catalytic dyad of the SARS-CoV-2 [M.sup.pro] substrate binding pocket, while two of them (geranylisobutanoate and 3- octane) are found to be the best hits that formed hydrogen bonds with [Glu.sup.166] and [Ser.sup.144] of SARS-CoV-2 [M.sup.pro]. Conclusion: Based on our in silico analysis, top hits from Thymus schimperi may serve as potential anti-SARS-CoV-2 compounds. Further in vitro and in vivo studies are recommended to characterize these compounds for clinical applications. Keywords: structural analysis, SARS-CoV-2, main protease, inhibitors, Thymus schimperi