Isolation and In Silico Anti-SARS-CoV-2 Papain-Like Protease Potentialities of Two Rare 2-Phenoxychromone Derivatives from Artemisia spp

Two rare 2-phenoxychromone derivatives, 6-demethoxy-4`-O-capillarsine ( ) and tenuflorin C ( ), were isolated from the areal parts of and respectively, for the first time. Being rare in nature, the inhibition potentialities of and against SARS-CoV-2 was investigated using multistage in silico techniques. At first, molecular similarity and fingerprint studies were conducted for and against co-crystallized ligands of eight different COVID-19 enzymes. The carried-out studies indicated the similarity of and with , the co-crystallized ligand of COVID-19 Papain-Like Protease (PLP), (PDB ID: 3E9S). Therefore, molecular docking studies of and 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 and against seven models indicated the general safety and the likeness of and to be drugs. Lastly, to authenticate the binding and to investigate the thermodynamic characters, molecular dynamics (MD) simulation studies were conducted on and PLP.