Discovery of Sphingosine-1-Phosphate Receptor Modulators as Potential CHI3L1 Inhibitors by Ligand-Based Virtual Screening and Molecular Dynamics Simulations.

Abstract

Multiple sclerosis is characterized by central nervous system inflammation, demyelination, and neuronal degeneration. Current diagnostic and prognostic methods lack precision, necessitating biomarkers for personalized treatment strategies. Chitinase 3-like 1 (CHI3L1) has emerged as a potential prognostic marker, with elevated levels correlating with disease severity and relapse risk. Despite its therapeutic potential, few CHI3L1 inhibitors have been identified. Using ligand-based virtual screening and molecular dynamics simulations, Food and Drug Administration-approved drugs have been screened as CHI3L1 inhibitors with the final goals of being repurposed in MS and other inflammatory diseases, offering promising therapeutic approaches. This investigation suggests that sphingosine-1-phosphate receptor modulators such as fingolimod could be potential inhibitors for CHI3L1.