The prevalence of Diabetes mellitus (DM) is continuously rising worldwide. Among its types, type I is characterized by the destruction of beta cells triggered by various mechanisms, including the activation of Caspase 3. Studies have demonstrated the crucial role of Caspase 3 in initiating the apoptosis of beta cells in DM. Our research aims to identify possible phytocompounds inhibitors of Caspase 3 using computational approach. We obtained 3D structures of Caspase 3 and 6511 phytocompounds from the Protein Data Bank and the African Natural Products Database, respectively. The phytocompounds were assessed for druglikeness properties, topological polar surface area, and preliminary toxicity using DataWarrior. The phytocompounds were subjected to molecular docking simulation (MDS) at Caspase 3 active site using AutoDock-Vina. The frontrunner phytocompounds obtained from the MDS were subjected to protease inhibition prediction on Molinspiration. The pharmacokinetics of the phytocompounds were assessed on SwissADME. The in-depth computational toxicity profile of the phytocompounds was evaluated on the pkCSM web. The binding interactions of the phytocompounds with Caspase 3 were assessed with Discovery Studio Visualizer and Maestro. Seventeen phytocompounds were found to have no violation of Lipinski's rule and had no toxicity based on the preliminary assessment, have better binding affinity and protease inhibitory prediction scores than the references, have optimistic bioactivity radar prediction and similar amino acids interaction, in comparison with the references. Further studies, which include in-vitro and in-vivo studies, will be carried out to validate the results of this study.

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 at beta-cells transplantation, but the cost and availability of donors pose a great challenge to the process. Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase A (DYRK1A) plays a crucial role in beta-cells destruction. Our research targets to identify plants that can be utilized as a possible alternative approach to beta-cell replacement through a pharmacologically induced regeneration of new beta-cells in-silico. The 3D structure DYRK1A and 6511 phytochemicals were obtained from the Protein Data Bank and the African Natural Products Database respectively. They were duly prepared for molecular docking simulations (MDS). MDS was implemented, after validation of docking protocols, in AutoDock-Vina®, with virtual screening scripts. Phytocompounds with good binding affinities for DYRK1A were selected as frontrunners. The compounds were screened for toxicity, Lipinski’s rule confirmation with Data Warrior software followed by kinase inhibitory bioactivity prediction with the Molinspiration Chemoinformatics web tool. Twelve phytocompounds were found to be predictably highly active in-silico against DYRK1A with good drug-like property based on Lipinski’s rule, non-mutagenic, non-tumorigenic, no reproductive effect, and non-irritant, with high predicted bioactivity. In-silico active phytocompounds against DYRK1A with their plant sources and physicochemical parameters were identified. Further studies will be carried out in-vitro and in-vivo to validate the results of this study using plants containing the identified phytocompounds.