Molecules (Mar 2022)

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

DOI
https://doi.org/10.3390/molecules27051636
Journal volume & issue
Vol. 27, no. 5
p. 1636

Abstract

Read online

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).

Keywords