Comparative transcriptomics and virtual screening reveal druggable targets and phytochemicals for atopic dermatitis, psoriasis, and vitiligo

Atopic dermatitis (AD), psoriasis (PsO), and vitiligo are chronic inflammatory and autoimmune skin disorders influenced by genetic and environmental factors. Emerging evidence suggests concurrence of these diseases, but due to lack of any comparative studies among the three diseases the common genetic relatedness still need to be deciphered. This study aims to identify common differentially expressed genes (DEGs) through comparative transcriptomic analysis of lesion vs non-lesion skin samples datasets which can helps to understand the genetic links underlying these disorders. RNA-Seq datasets were obtained for three disorders from NCBI-SRA. After the data pre-processing, quality control, and read alignment, DEGs were identified using DESeq2 package. The significant DEGs were filtered by selecting the FDR and logFC parameters values to < 0.05 and ≥ 1, respectively. Gene Ontology (GO) and KEGG pathway enrichment analyses, and protein-protein interaction (PPI) networks were constructed. Moreover, Hub genes were identified using Cytohubba, and gene-disease associations were explored using DisGeNET and NetworkAnalyst. Our analysis identified 60 common DEGs (cDEGs) across AD, PsO, and vitiligo, including key hub genes such as RSAD2, IFIT3, OAS1, OAS2, GBP1, XAF1, CXCL10, IFI27, IFI44, and RTP4. These genes are primarily involved in immune response pathways, antiviral defense, and interferon signaling, suggesting their critical roles in the pathogenesis of these skin disorders. AI-driven target prioritization identified CXCL10 and TNFSF10 as promising druggable targets among the top hub genes. Virtual screening of 2015 phytochemicals from the IMPPAT database, followed by MD simulations and MM/PBSA free-energy evaluation, revealed Bismurrayaquinone A (-8.1 kcal/mol) and Withanolide G (-8.8 kcal/mol) as the most potent binders. ADMET prediction further established their potential as prospective modulators. These findings provide insight into the common genetic etiology of AD, PsO, and vitiligo and highlight two phytochemicals with promising therapeutic potential for future experimental validation.