In-silico inhibition of galectin-1 during HIV-1 pathogensis: a pharmacophore based virtual screening, molecular docking & qsar studies

Abstract

Galectin-1 helps in HIV-1 pathogenesis by interaction between viral capsid protein gp120 and CD4 protein of susceptible helper T cell. Therefore, strategy to identify inhibitor for Galectin-1 will be of much importance in medical research. Here, structure based pharmacophore modelling, pharmacophore based screening, molecular docking, protein–ligand interaction fingerprints, binding energy calculations, and Quantitative Structure-Activity Relationship (QSAR) predictions were employed in a virtual screening strategy to identify novel inhibitors. A structure-based pharmacophore model was hypothesized that contained 6 pharmacophoric features as observed in crystal structure of galectin-1 and its inhibitor thiodigalactoside. The pharmacophore model was used to screen NCI, open database compounds release4 with 2, 46,374 active molecules. A total of 2233 hits were obtained from NCI database. The hits retrieved were further screened by molecular docking, protein–ligand interaction fingerprints, binding energy calculations. After that we predicted IC50 values of screened molecules. Based on these results, 6 molecules were predicted as potential inhibitors of galectin-1.