IN SILICO SCREENING OF NATURAL COMPOUNDS AGAINST MULTIPLE DISEASE-ASSOCIATED PROTEINS IN VITILIGO: A MULTI-TARGET STRATEGEY FOR VITILIGO THERAPY

Abstract

: This study aims to explore the potential of natural phytochemicals in the treatment of vitiligo by targeting multiple disease-associated proteins through in silico methodologies. Vitiligo is a multifactorial autoimmune disorder characterized by the loss of melanocytes, leading to depigmented skin patches.The complexity of its pathogenesis, involving oxidative stress, immune dysregulation, and melanocyte dysfunction, poses significant challenges for effective therapeutic interventions. Emerging evidence suggests that targeting multiple disease-associated proteins simultaneously may offer a more comprehensive therapeutic approach. In this study, we employed an in silico multi target drug discovery strategy to identify potential natural compounds capable of modulating key proteins implicated in vitiligo pathogenesis. By screening a diverse library of phytochemicals against selected targets such as IFNG, HSP70, and pro-inflammatory cytokines IL-6,IL-23,we aimed to elucidate compounds with favorable binding affinities and pharmacokinetic properties. Subsequent molecular docking, ADMET profiling, and molecular dynamics simulations were conducted to assess the stability and efficacy of these interactions. This comprehensive computational approach aspires to uncover promising natural compounds that can be further developed into effective multi target therapeutics for vitiligo management. Results In this study,selected phytochemicals was screened against vitiligo-associated proteins: Jak1,HSP70,interleukin-6 (IL-6). Molecular docking identified WithaferinA as top candidates out of selected naturalcompounds that exhibit strong binding affinities against each target protein.Subsequent ADMET profiling indicated that these compounds possess favorable pharmacokinetic properties, including high gastrointestinal absorption and compliance with Lipinski's Rule of Five, suggesting good oral bioavailability and safety profiles.This demonstrated to be the best potent inhibitor of Vitiligo associated proteins. Conclusion This in silico investigation underscores the potential of natural phytochemicals as multi-target therapeutic agents for vitiligo. Through comprehensive computational analyses—including molecular docking, ADMET profiling —compounds such as WithaferinA demonstrated strong binding affinities(-10.4,-11.5,6.9) Kcal/mol to key targets proteins implicated in vitiligo pathogenesis,Further analysis of the same can be conducted to ratify the computational approach