Jusanin, a New Flavonoid from 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
Author Information
Yerlan M Suleimen: The International Centre for Interdisciplinary Solutions on Antibiotics and Secondary Metabolites, Republican Collection of Microorganisms, Nur-Sultan 010000, Kazakhstan. ORCID
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. ORCID
Margarita Y Ishmuratova: Department of Botany, E.A. Buketov Karaganda University, Karaganda 100024, Kazakhstan. ORCID
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. ORCID
Bshra A Alsfouk: Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia. ORCID
Eslam B Elkaeed: Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Riyadh 13713, Saudi Arabia. ORCID
Ibrahim H Eissa: Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt. ORCID
Ahmed M Metwaly: Pharmacognosy and Medicinal Plants Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt. ORCID
A new flavonoid, Jusanin, () has been isolated from the aerial parts of . 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 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 and , 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 and . Accordingly, molecular docking studies of against the target enzyme have been achieved and showed that 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 M-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 (), methyl-3-[S-hydroxyprenyl]-cumarate (), and β-sitosterol ().
