UNVEILING DYSREGULATED GENE EXPRESSION ANALYSIS IN VITILIGO AND A COMPUTATIONAL APPROACH FOR IDENTIFYING PROMISING DRUG TARGETS

Abstract

Vitiligo is a chronic autoimmune disease characterized by the destruction or dysfunction of melanocytes, leading to the emergence of depigmented white patches on various parts of the body. Firstly, focusing on the gene expression of genes implicated in vitiligo and in further study the genes that exhibit overexpression or under expression in this disease, using the Gene Expression Omnibus (GEO) database were observed. To accomplish this, various analytical techniques such as volcano plots, mean-difference plots, and box plots were employed to explore the involvement of these genes in the disease pathology. Based on the dataset analysis, a set of ten up-regulated and ten down-regulated genes were carefully selected for further investigation. In order to stabilize these genes, potential inhibitors, small molecules, or drugs were identified through the drug gene budger. Additionally, a protein known as 6AAH, which acts as a JAK-STAT inhibitor, was chosen after from the Protein Data Bank (PDB) and its structural characteristics were observe using Pymol. Following these preliminary steps, therapeutic intervention using Carica papaya, a medicinal plant, was explored for its potential in vitiligo treatment. Five specific phytochemicals were selected, and evaluate their binding energies with the 6AAH protein through molecular docking using MGL AutoDock. Furthermore, the blood-brain barrier (BBB) permeability of these compounds was assessed using SWISS-ADME to ensure their safety and efficacy. Among the tested phytochemicals, riboflavin demonstrated the most promising results in terms of binding affinity with the 6AAH protein. To optimize the outcomes, Poserlean, another medicinal plant, was selected, and its toxicity, BBB permeability, and interaction with the 6AAH protein were evaluated using MGL AutoDock. To validate and consolidate the findings, extensive simulations were performed to enhance the clarity and comprehensibility of the obtained results.