In Silico Study of Coumarins: Wedelolactone as a Potential Inhibitor of the Spike Protein of the SARS-CoV-2 Variants

Despite the rigorous global efforts to control SARS-CoV-2 transmission, it continues to pose a serious threat to humans with the frequent emergence of new variants. Thus, robust therapeutics to combat the virus are a desperate need. The SARS-CoV-2 spike (S) protein is an important target protein as it mediates the entry of the virus inside the host cells, which is initiated by the binding of the receptor-binding domain (RBD) to its cognate receptor, angiotensin-converting enzyme 2 (ACE-2). Herein, the inhibition potential of several naturally occurring coumarins was investigated against the spike proteins of SARS-CoV-2 variants using computational approaches. Molecular docking studies revealed 26 coumarins with better binding energies than the reference ligands, molnupiravir and ceftazidime, against the S-RBD of the omicron variant. The top 10 best-docked coumarins were further analyzed to understand their binding interactions against the spike proteins of other variants (wild-type, Alpha, Beta, Gamma, and Delta), and these studies also demonstrated decent binding energies. Physicochemical, QSAR, and pharmacokinetics analyses of the coumarins revealed wedelolactone as the best inhibitor of the spike protein with ideal Lipinski's drug-likeness and optimal ADMET properties. Furthermore, coarse-grained molecular dynamics (MD) simulation studies of spike protein-wedelolactone complexes validated the stable binding of wedelolactone in the respective binding pockets. As an outcome, wedelolactone could be utilized to develop a potent drug candidate against COVID-19 by blocking the viral entry into the host cell. [ FROM AUTHOR]

Potential roles of medicinal plants for the treatment of viral diseases focusing on COVID-19: A review.

The whole world is entangled by the coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), people are dying in thousands each day, and without an actual medication, it seems not possible for the bringing this global health crisis to a stop. Natural products have been in constant use since ancient times and are proven by time to be effective. Crude extract or pure compounds isolated from medicinal plants and/or herbs such as Artemisia annua, Agastache rugosa, Astragalus membranaceus, Cassia alata, Ecklonia cava, Gymnema sylvestre, Glycyrrhizae uralensis, Houttuynia cordata, Lindera aggregata, Lycoris radiata, Mollugo cerviana, Polygonum multiflorum, Pyrrosia lingua, Saposhnikoviae divaricate, Tinospora cordifolia etc. have shown promising inhibitory effect against coronavirus. Several molecules, including acacetin, amentoflavone, allicin, blancoxanthone, curcumin, daidzein, diosmin, epigallocatechin-gallate, emodin, hesperidin, herbacetin, hirsutenone, iguesterin, jubanine G, kaempferol, lycorine, pectolinarin, phloroeckol, silvestrol, tanshinone I, taxifolin, rhoifolin, xanthoangelol E, zingerol etc. isolated from plants could also be potential drug candidates against COVID-19. Moreover, these could also show promising inhibitory effects against influenza-parainfluenza viruses, respiratory syncytial virus, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have reported 93 antiviral drug candidates which could be a potential area of research in drug discovery.