Jusanin, a New Flavonoid from <i>Artemisia commutata</i> with an In Silico Inhibitory Potential against the SARS-CoV-2 Main Protease
Yerlan M. Suleimen,
Rani A. Jose,
Raigul N. Suleimen,
Christoph Arenz,
Margarita Y. Ishmuratova,
Suzanne Toppet,
Wim Dehaen,
Bshra 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
Christoph Arenz
Institut für Chemie der Humboldt-Universität zu, D-12489 Berlin, Germany
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
Bshra 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 flavonoid, Jusanin, (1) has been isolated from the aerial parts of Artemisia commutata. The chemical structure of Jusanin has been elucidated using 1D, 2D NMR, and HR-Ms spectroscopic methods to be 5,2′,4′-trihydroxy-6,7,5′-trimethoxyflavone. Being new in nature, the inhibition potential of 1 has been estimated against SARS-CoV-2 using different in silico techniques. Firstly, molecular similarity and fingerprint studies have been conducted for Jusanin against co-crystallized ligands of eight different SARS-CoV-2 essential proteins. The studies indicated the similarity between 1 and X77, the co-crystallized ligand SARS-CoV-2 main protease (PDB ID: 6W63). To confirm the obtained results, a DFT study was carried out and indicated the similarity of (total energy, HOMO, LUMO, gap energy, and dipole moment) between 1 and X77. Accordingly, molecular docking studies of 1 against the target enzyme have been achieved and showed that 1 bonded correctly in the protein’s active site with a binding energy of −19.54 Kcal/mol. Additionally, in silico ADMET in addition to the toxicity evaluation of Jusanin against seven models have been preceded and indicated the general safety and the likeness of Jusanin to be a drug. Finally, molecular dynamics simulation studies were applied to investigate the dynamic behavior of the Mpro-Jusanin complex and confirmed the correct binding at 100 ns. In addition to 1, three other metabolites have been isolated and identified to be сapillartemisin A (2), methyl-3-[S-hydroxyprenyl]-cumarate (3), and β-sitosterol (4).
