Discovery of natural orexin 2 receptor antagonists from Valeriana species: A potential approach for insomnia treatment

approach to identify natural OX2R antagonists from Valeriana species. Phytochemicals were screened based on molecular docking and favourable ADME/T profiles. Molecular dynamics (MD) simulations and post-MD analysis confirmed stable binding of hesperidine and valerosidate to OX2R. Principal component analysis (PCA) revealed minimal conformational variability while gibbs free energy landscape (FEL) analysis and MM-PBSA binding free energy calculations further supported the strong binding of hesperidine and valerosidate to OX2R, comparable to suvorexant. These findings support hesperidine and valerosidate as promising, naturally derived OX2R antagonists, and warrant further invitro and invivo investigations for potential therapeutic application in insomnia treatment.