Targeting the sphingosine 1-phosphate receptor 2 for multiple sclerosis computer-aided drug discovery

• Main Authors: Dalmacio, Jeremy V., Tanada, Noah Rafael Moran
• Format: text
• Language: English
• Published: Animo Repository 2022
• Subjects: Drugs—Computer-aided design; Multiple sclerosis—Treatment; Biochemistry, Biophysics, and Structural Biology
• Online Access: https://animorepository.dlsu.edu.ph/etdb_chem/23; https://animorepository.dlsu.edu.ph/cgi/viewcontent.cgi?article=1026&context=etdb_chem
• Institution: De La Salle University

Multiple sclerosis (MS) continues to affect 2.8 million people worldwide in 2020, and as of yet there is no cure for it. There exist drugs to treat the symptoms of MS, but those that aim to treat the cause of the disease are scarce, as it affects the autoimmune response, and little is known about diseases of this type. Computer-aided drug design (CADD) is a viable method for discovering new drugs, being more cost-effective and efficient than traditional methods, alleviating the need for numerous clinical trials. It can be utilized in discovering hits that can potentially target MS as well. This paper discusses the current state of MS, and the application of computational techniques, and methods in discovering a new drug for it. We utilized various computational software for the visualization of protein and ligand structures, docking simulations and virtual screening, clustering, ADME, and the analysis of top hits in order to discover a drug specifically targeting the sphingolipid-1 receptors (S1PR). Two compounds, trimethyl-[4-[(5-methyl-1,2-oxazol-3-yl)oxy]but-2-ynyl]azanium (Compound 1) and 3-tert-butyl-8-methyl-1-oxa-3,8-diazaspiro[4.5]decane-2,4-dione (Compound 2) were selected for molecular dynamics (MD) simulations, and subsequent analyses to determine their effectiveness in binding to S1PR2.