Virtual screening using pharmacophores model and molecular dynamic simulation for FDA-approved natural drugs repurposing as inhibitors of lysosomal alpha-glucosidase associated with type II diabetes

Diabetes mellitus (DM) is a common chronic illness that is acknowledged as a major public health issue. A family of drugs called alpha-glucosidase inhibitors is used to treat diabetes. It works by slowing down the digestion of carbs, which delays the absorption of glucose. Voglibose, miglitol, and acarbose are only a few examples. As such, current efforts are concentrated on finding novel inhibitors that have negligible or no negative effects. Utilizing a variety of bioinformatics techniques, an effective lysosomal alpha-glucosidase inhibitor was found. Alpha-glucosidase's 3D structure, designated by PDB ID 5KZX, was acquired from the RCSB PDB. Virtual screening using pharmacophores was made easier by Pharmit software; flavonoids were chosen because they have the potential to be highly effective alpha-glucosidase inhibitors. Using AutoDock Vina via Pyrx, docking was carried out, and BIOVIA Discovery Studio was used to assess compound-target protein binding interactions. Using Desmond molecular dynamics simulation (MD), the stability of protein-inhibitor complexes in physiological conditions was examined. The newly chosen chemical's absorption and ADMET qualities were improved by further investigation. Two newly identified scientific inhibitors that block the receptor's function were found as a result of the investigation. This result might aid in the creation of a novel medication for type II diabetes and is significant for the scientific community. A potential inhibitor with more efficacy and fewer side effects turned out to be the lead chemical. This study makes it easier to test the chemical further and determine how effective it is against alpha-glucosidase.