Virtual screening and molecular dynamics simulation study of abyssomicins as potential inhibitors of COVID-19 virus main protease and spike protein.

The lack of any effective cure for the infectious COVID-19 disease has created a sense of urgency and motivated the search for effective antiviral drugs. Abyssomicins are actinomyces-derived spirotetronates polyketides antibiotics known for their promising antibacterial, antitumor, and antiviral activities. In this study, computational approaches were used to investigate the binding mechanism and the inhibitory ability of 38 abyssomicins against the main protease (Mpro) and the spike protein receptor-binding domain (RBD) of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The results identified abyssomicins C, J, W, atrop-O-benzyl abyssomicin C, and atrop-O-benzyl desmethyl abyssomicin C as the most potential inhibitors of Mpro and RBD with binding energy ranges between -8.1 and -9.9 kcal mol-1; and between -6.9 and -8.2 kcal mol-1, respectively. Further analyses of physicochemical properties and drug-likeness suggested that all selected active abyssomicins, with the exception of abyssomicin J, obeyed Lipinski's rule of five. The stability of protein-ligand complexes was confirmed by performing molecular dynamics simulation for 100 ns and evaluating parameters such as such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent accessible surface area (SASA), total number of contacts, and secondary structure. Prime/MM-GBSA (Molecular Mechanics-General Born Surface Area) and principal component analysis (PCA) analyses also confirmed the stable nature of protein-ligand complexes. Overall, the results showed that the studied abyssomicins have significant interactions with the selected protein targets; therefore, they were deemed viable candidates for further in vitro and in vivo evaluation. Communicated by Ramaswamy H. Sarma.

Salvadora persica L.: Toothbrush tree with health benefits and industrial applications - An updated evidence-based review.

Salvadora persica L. is also known as Arak (in Arabic) and Peelu (in Urdu). Its frequent use as a toothbrush (miswak) is highly recommended by Prophet Muhammad. With a long history in folk medicine for centuries, S. persica was used in oral hygiene, food, cosmetics, fuel, and even as a medicine. Previous phytochemical investigation of its different parts afforded different classes of secondary metabolites such as flavonoids, glycosides, sterols, terpenes, carbohydrates and alkaloids. Organic sulfur-containing compounds and elemental sulfur are also present. In addition, there is a huge research on its biological potentials and industrial applications. Many pharmacological activities were reported experimentally, including antimicrobial, antioxidant, analgesic, anthelmintic, anti-inflammatory, antiulcer, sedative, anticonvulsant, anti-osteoporosis, antidiabetic, hypo-lipidemic, in addition to wound-healing, antidepressant and antitumor activities. Recently, a possible activity against COVID-19 protease was documented by molecular docking. This review tries to provide a recent detailed documentation of folk and modern uses of S. persica, focusing on the possible relations between its chemical constituents, pharmacological properties, and industrial applications. Moreover, a brief about recent analytical and validation methods for the major antimicrobial component is reported.