Abstract:
Two rare 2-phenoxychromone derivatives, 6-demethoxy-4‘-O-capillarsine (1) and tenuflorin
C (2), were isolated from the areal parts of Artemisia commutata and A. glauca, respectively, for the
first time. Being rare in nature, the inhibition potentialities of 1 and 2 against SARS-CoV-2 was
investigated using multistage in silico techniques. At first, molecular similarity and fingerprint
studies were conducted for 1 and 2 against co-crystallized ligands of eight different COVID-19
enzymes. The carried-out studies indicated the similarity of 1 and 2 with TTT, the co-crystallized
ligand of COVID-19 Papain-Like Protease (PLP), (PDB ID: 3E9S). Therefore, molecular docking
studies of 1 and 2 against the PLP were carried out and revealed correct binding inside the active
site exhibiting binding energies of −18.86 and −18.37 Kcal/mol, respectively. Further, in silico
ADMET in addition to toxicity evaluation of 1 and 2 against seven models indicated the general
safety and the likeness of 1 and 2 to be drugs. Lastly, to authenticate the binding and to investigate
the thermodynamic characters, molecular dynamics (MD) simulation studies were conducted on 1
and PLP.
