In silico analysis to identify potential antitubercular molecules in Morus alba through virtual screening and molecular dynamics simulations.

A major obstacle in the treatment of tuberculosis (TB) is to combat the emerging resistant strains of its causing agent i.e. Mycobacterium tuberculosis (MTb). The emergence of multidrug-resistant and extensively drug-resistant -TB strains raise a requirement of new potential anti-tubercular compounds. In this direction, different plant parts of Morus alba were tested against MTb and found to be active with a minimum inhibitory concentration ranging between 125 µg/ml to 31.5 µg/ml. Further to identify the phytochompounds having anti-mycobacterium activity, phytocompounds of the plant were docked against the five MTb proteins (PDB ID: 3HEM, 4OTK, 2QO0, 2AQ1 and 6MNA). Among twenty-two tested phytocompounds, four phytocompounds with effective binding energy (kcal/mol): Petunidin-3-rutinoside (3HEM: -8.2, 4OTK: -6.9, 2QO0: -9.0, 2AQ1: -8.3 and 6MNA:-7.8), Quercetin-3'-glucoside (3HEM:-6.7, 4OTK:-7.6, 2QO0:-7.6, 2AQ1:7.6 and 6MNA:-6.4), Rutin (3HEM:-7.8, 4OTK:-7.5, 2QO0:-9.1, 2AQ1:9.3 and 6MNA:-6.9) and Isoquercitrin (3HEM:-7.3, 4OTK:-6.6, 2QO0:-7.7, 2AQ1:8.3 and 6MNA:-6.6) shows promising activity against all the five target proteins. Further molecular dynamics studies of Petunidin-3-rutinoside with three target proteins 3HEM, 2AQ1 and 2QO0 resulted with low values of average RMSD (3.723 Å, 3.261 Å, and 2.497 Å, respectively) show that the complexes have better conformational stability. The wet lab validation of the current study will pave the new dimensions for the cure of TB patients.Communicated by Ramaswamy H. Sarma.

In Silico Studies Reveal Antiviral Effects of Traditional Indian Spices on COVID-19.

BACKGROUND: The global health emergency due to SARS-CoV-2 causing the COVID-19 pandemic emphasized the scientific community to intensify their research work for its therapeutic solution. In this study, Indian traditional spices owing to various medicinal properties were tested in silico for their inhibitory activity against SARS-CoV-2 proteins. SARS-CoV-2 spike proteins (SP) and main proteases (Mpro) play a significant role in infection development were considered as potential drug targets. METHODS: A total of 75 phytochemicals present in traditional Indian spices retrieved from the published literature and Dr. Duke's Phytochemical and Ethnobotanical Database, were docked with Mpro (PDB IDs: 6YNQ), and the SP (PDB IDs: 6LXT and 6YOR). RESULTS: Through the screening process, 75 retrieved phytochemicals were docked with spike protein (PDB IDs: 6LXT and 6YOR) and main protease (PDB ID: 6YNQ) of SARS-CoV-2. Among them, myricetin, a flavonoid (rank score: 6LXT: -11.72383; 6YOR: -9.87943; 6YNQ: -11.68164) from Allium sativum L and Isovitexin, an example of flavone (rank score: 6LXT: -12.14922; 6YOR: -10.19443; 6YNQ: -12.60603) from Pimpinella anisumL were the most potent ligands against SP and Mpro of SARS-CoV-2. Whereas, Astragalin from Crocus sativus L.; Rutin from Illicium verum, Oxyguttiferone from Garcinia cambogia; Scopolin from Apium graveolens L, Luteolin from Salvia officinalis, Emodin, Aloe-emodin from Cinnamomum zeylanicium and Apigenin from Allium sativum L showed better inhibition against Mpro than SP of SARS-CoV-2. The amino acid residues like SER, LYS, ASP and TYR were found playing important role in protein-ligand interactions via hydrogen bonding and Vander Waals forces. CONCLUSION: Optimal use of traditional spices in our daily meals may help fight against COVID-19. This study also paves the path for herbal drug formulation against SARS-CoV-2 after wet lab validation.