In silico Screening of Potential SARS-CoV-2 Main Protease Inhibitors from Thymus schimperi

• Published in: Advances and applications in bioinformatics and chemistry Vol. 16; pp. 1 - 13
• Main Authors: Mengist, Hylemariam Mihiretie, Khalid, Zunera, Adane, Fentahun
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 2023; Taylor & Francis Ltd; Dove; Dove Medical Press
• Subjects: Analysis; Antiviral agents; Antiviral drugs; Binding sites; Bioavailability; Carcinogenicity; Chinese medicine; Composition; Coronaviruses; COVID-19; Cytotoxicity; Disease transmission; Drugs; Enzymes; Essential oils; Growth; Health aspects; Hepatitis; Hepatotoxicity; Herbal medicine; Hydrogen bonding; Immunotoxicity; inhibitors; Ligands; main protease; Molecular dynamics; Mutagenicity; Oils & fats; Original Research; Phytochemicals; Pinene; Protease inhibitors; Proteinase inhibitors; Proteins; RNA polymerase; sars-cov-2; Severe acute respiratory syndrome coronavirus 2; structural analysis; Thymes; Thymus gland; Thymus schimperi; Ethiopia; inhibitors; SARS-CoV-2; Thymus schimperi; structural analysis; main protease
• ISSN: 1178-6949; 1178-6949
• DOI: 10.2147/AABC.S393084

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 ) inhibitors extracted from the essential oil of which could contribute to the discovery of potent anti-SARS-CoV-2 phytochemicals. 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. All compounds exhibited a bioavailability score of ≥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 substrate binding pocket, while two of them (geranylisobutanoate and 3-octane) are found to be the best hits that formed hydrogen bonds with Glu and Ser of SARS-CoV-2 M . Based on our in silico analysis, top hits from 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.