Isolation and In Silico Anti-SARS-CoV-2 Papain-Like Protease Potentialities of Two Rare 2-Phenoxychromone Derivatives from Artemisia spp.
E. M. Suleimen, Rani Alphonsa Jose, Raigul N. Suleimen, Christoph Arenz, Margarita Ishmuratova, Suzanne Toppet, Wim Dehaen, Aisha A. Alsfouk, Eslam B. Elkaeed, Ibrahim H. Eissa, Ahmed M. Metwaly
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.