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

E. M. Suleimen, Rani Alphonsa Jose, Raigul N. Suleimen, Margarita Ishmuratova, Suzanne Toppet, Wim Dehaen, Aisha A. Alsfouk, Eslam B. Elkaeed, Ibrahim H. Eissa, Ahmed M. Metwaly

Molecules, 2022

Full text Open access: Gold Metadata (CSL-JSON)
DOI 10.3390/molecules27072281
Data confidence 85 high
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Abstract

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).