Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disease with rising prevalence, marked by eczematous lesions, itching, and a weakened skin barrier often tied to filaggrin gene mutations. This breakdown allows allergen and microbe entry, with thymic stromal lymphopoietin (TSLP) playing a crucial role by activating immune pathways that amplify the allergic response. TSLP's central role in AD pathogenesis makes it a promising therapeutic target. Consequently, in this study, we used the virtual drug screening, molecular dynamics simulation, and binding free energies calculation approaches to explore the African Natural Product Database against the TSLP protein. The molecular screening identified four compounds with high docking scores, namely SA_0090 (-7.37), EA_0131 (-7.10), NA_0018 (-7.03), and WA_0006 (-6.99 kcal/mol). Furthermore, the KD analysis showed a strong binding affinity of these compounds with TSLP, with values of -5.36, -5.36, -5.34, and -5.32 kcal/mol, respectively. Moreover, the strong binding affinity of these compounds was further validated by molecular dynamic simulation analysis, which revealed that the WA_0006-TSLP is the most stable complex with the lowest average RMSD. However, the total binding free energies were -40.5602, -41.0967, -27.3293, and -51.3496 kcal/mol, respectively, showing the strong interaction between the selected compounds and TSLP. Likewise, these compounds showed excellent pharmacokinetics characteristics. In conclusion, this integrative approach provides a foundation for the development of safe and effective treatments for AD, potentially offering relief to millions of patients worldwide.