In-silico Study for African Plants with Possible Beta-Cell Regeneration Effect through Inhibition of DYRK1A

Background: The continuous destruction of normal insulin-producing pancreatic beta cells is a contributing factor in all common forms of diabetes, due to insufficient production of insulin, especially in type 1 diabetes. There are attempts to beta- cells transplantation, but the cost and availability of donors pose a great challenge to the process. Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase A plays a crucial role in beta-cells destruction. Aims: Our research targets to identify plants for that can be utilized possible alternative approach of beta-cell replacement through a pharmacologically induced regeneration of new beta cells in-silico. Methods and Material: The 3D structure Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase A and 6511 phytochemicals were obtained from Protein Databank and African Natural Products Database respectively. They were appropriately prepared for molecular docking simulations. Molecular docking simulations were implemented, after validation of docking protocols, in AutoDock-Vina®, using virtual screening scripts. Phytocompounds with good binding affinities for Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase A were selected as frontrunners. The compounds were screened for toxicity and Lipinski's rule confirmation using Datawarrior and then kinase inhibitory bioactivity prediction using Molinspiration. Results: Twelve phytocompounds were found to be predictably highly active in-silico against Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase A, druglike based on Lipinski's rule, non-mutagenic, non-tumorigenic, no reproductive effect and non-irritant, with high bioactivity prediction. Conclusions: In-silico active phytocompounds against Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase A with their plant sources and physicochemical parameters were identified. Further studies will be carried out in-vitro and in-vivo in to validate the results of this study using plants containing the identified phytocompounds