In Silico Screening of Rauwolfia Serpentina Phytochemicals as Orexin Receptor-2 Agonists for the Management of Narcolepsy
Pawan Yadav
Government Medical College, Amritsar, Punjab, India.
Mohammad Azram
Government Medical College, Amritsar, Punjab, India.
Mohd Faraz
Department of Radiodiagnosis, Paramedical College, JN Medical College, Aligarh Muslim University, Aligarh, India.
Nadeem
Department of Radiodiagnosis, Paramedical College, JN Medical College, Aligarh Muslim University, Aligarh, India.
Kashif Abbas
Department of Zoology, Aligarh Muslim University, Aligarh, India.
Mohd Mustafa
Department of Biochemistry, J.N. Medical College, Aligarh Muslim University, Aligarh, India.
Mudassir Alam
*
Indian Biological Sciences and Research Institute (IBRI), Noida, India.
Sarfaraz Khan
Department of Botany, MJPRU, Bareilly, India.
*Author to whom correspondence should be addressed.
Abstract
The neuropeptide orexin/hypocretin plays a crucial role in numerous physiological processes such as regulation of sleep/wakefulness, appetite and emotions. Dysregulation of orexin signaling has been implicated in hypersomnia, especially in narcolepsy, characterized by excessive daytime sleepiness (EDS), sudden loss of muscle tone while awake (cataplexy), sleep paralysis, and hallucinations. Lack of orexins contributes to the development of narcolepsy, thus small-molecule orexin receptor agonists are promising therapeutics for narcolepsy. In this study, we employed several bioinformatics tools to screen and identify effective phytochemicals of Rauvolfia serpentina that may act as Orexin 2 receptor (OX2R) agonists. In silico methods such as protein‒ligand interaction analysis, drug‒likeness evaluation, ADMET analysis, molecular docking, molecular dynamics simulation, and biological activity prediction, have been employed extensively. Among all screened phytochemicals from R. serpentina, both tetraphylline and yohimbine were identified as promising drug candidates due to their favorable ADMET profile, high docking scores, permeability of the blood‒brain barrier, and significant RMSD, RMSF, Rg, and SASA values. However, the study is solely based on in silico study, therefore in vitro and in vivo experimental studies are suggested to validate the potency and efficacy of these medications.
Keywords: Orexin, Narcolepsy, Rauwolfia serpentina, In silico, ADMET, MD simulation