Unravelling the protective effects of peptide isolated from marine sponge extract MS01 against SH-SY5Y cell line and its in-silico pharmacokinetic analysis

Abstract

Parkinson's disease (PD) is characterised by developing postural instability, resting seizures, tremors, and a movement problem coupled with stiffness. All the available drugs can improve motor function considerably, but they can also have negative side effects, especially if the problem gets worse. The structure-activity relation was performed in the DISCOVERY STUDIO V2.5.5 pharmacophore model using the HypoGen algorithm for a training set of 15 compounds. Here, xenin peptide fits well with a least cost difference and a fit value of 10.46, indicating a favourable pharmacological characteristic. Therefore, we tried applying gene network analysis in cytoHubba to find the hub gene for PD in Danio rerio and Homo sapiens, as zebrafish and humans share many disease proteins and processes. Molecular docking studies for the hub gene polyubiquitin B from Danio rerio and Parkin from Homo sapiens, as well as the peptide xenin obtained from the marine sponge extract MS01 was performed. The peptide exhibits a substantial binding affinity with the receptor UBB through 8 and PRKN through 4 intermolecular hydrogen bonds in their bonded and non-bonded interactions, although it has little effect on the protein structure, according to simulation studies and dynamical free energy calculations. The protein structure has also been stabilised in terms of energy, secondary structure, and flexibility by the peptide binding. In addition to in-silico analysis the extract was tested in-vitro on SH-SY5Y cells for its effectiveness against ROS and cell viability, which proved its qualitative effect.