Abstract:
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 5,20
,40
-trihydroxy-6,7,50
-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).
