Isolation and In Silico SARS-CoV-2 Main Protease Inhibition Potential of Jusan Coumarin, a New Dicoumarin from Artemisia glauca

• Main Authors: Alsfouk, A.A (Author), Dehaen, W. (Author), Eissa, I.H (Author), Elkaeed, E.B (Author), Ishmuratova, M.Y (Author), Jose, R.A (Author), Metwaly, A.M (Author), Suleimen, R.N (Author), Suleimen, Y.M (Author), Toppet, S. (Author)
• Format: Article
• Language: English
• Published: MDPI 2022
• Subjects: 3C-like proteinase, SARS-CoV-2; ADMET; Artemisia; Artemisia glauca; chemistry; Coronavirus 3C Proteases; coumarin; coumarin derivative; Coumarins; COVID-19; COVID-19 main protease; DFT; dicoumarol; Dicumarol; drug therapy; jusan coumarin; ligand; Ligands; molecular docking; Molecular Docking Simulation; molecular dynamics; Molecular Dynamics Simulation; molecular similarity; new dicoumarin; Protease Inhibitors; proteinase inhibitor; SARS-CoV-2; structure fingerprint; toxicity
• Online Access: View Fulltext in Publisher

 A new dicoumarin, jusan coumarin, (1), has been isolated from Artemisia glauca aerial parts. The chemical structure of jusan coumarin was estimated, by 1D, 2D NMR as well as HR-Ms spectroscopic methods, to be 7-hydroxy-6-methoxy-3-[(2-oxo-2H-chromen-6-yl)oxy]-2H-chromen-2-one. As the first time to be introduced in nature, its potential against SARS-CoV-2 has been estimated using various in silico methods. Molecular similarity and fingerprints experiments have been utilized for 1 against nine co-crystallized ligands of COVID-19 vital proteins. The results declared a great similarity between Jusan Coumarin and X77, the ligand of COVID-19 main protease (PDB ID: 6W63), Mpro . To authenticate the obtained outputs, a DFT experiment was achieved to confirm the similarity of X77 and 1. Consequently, 1 was docked against Mpro . The results clarified that 1 bonded in a correct way inside Mpro active site, with a binding energy of −18.45 kcal/mol. Furthermore, the ADMET and toxicity profiles of 1 were evaluated and showed the safety of 1 and its likeness to be a drug. Finally, to confirm the binding and understand the thermodynamic characters between 1 and Mpro, several molecular dynamics (MD) simulations studies have been administered. Additionally, the known coumarin derivative, 7-isopentenyloxycoumarin (2), has been isolated as well as β-sitosterol (3). © 2022 by the authors. Licensee MDPI, Basel, Switzerland.