Isolation and In Silico SARS-CoV-2 Main Protease Inhibition Potential of Jusan Coumarin, a New Dicoumarin from <i>Artemisia glauca</i>
Yerlan M. Suleimen,
Rani A. Jose,
Raigul N. Suleimen,
Margarita Y. Ishmuratova,
Suzanne Toppet,
Wim Dehaen,
Aisha A. Alsfouk,
Eslam B. Elkaeed,
Ibrahim H. Eissa,
Ahmed M. Metwaly
Affiliations
Yerlan M. Suleimen
The International Centre for Interdisciplinary Solutions on Antibiotics and Secondary Metabolites, Republican Collection of Microorganisms, Nur-Sultan 010000, Kazakhstan
Rani A. Jose
Molecular Design & Synthesis, Department of Chemistry, Catholic University of Leuven, B-3001 Leuven, Belgium
Raigul N. Suleimen
Department of Technical Physics, Faculty of Physics and Technology, L.N. Gumilyov Eurasian National University, Nur-Sultan 010010, Kazakhstan
Margarita Y. Ishmuratova
Department of Botany, E.A. Buketov Karaganda University, Karaganda 100024, Kazakhstan
Suzanne Toppet
Molecular Design & Synthesis, Department of Chemistry, Catholic University of Leuven, B-3001 Leuven, Belgium
Wim Dehaen
Molecular Design & Synthesis, Department of Chemistry, Catholic University of Leuven, B-3001 Leuven, Belgium
Aisha A. Alsfouk
Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia
Eslam B. Elkaeed
Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Riyadh 13713, Saudi Arabia
Ibrahim H. Eissa
Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt
Ahmed M. Metwaly
Pharmacognosy and Medicinal Plants Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt
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).
