Pharmacophore Modeling, Docking, and Principal Component Analysis Based Clustering: Combined Computer-Assisted Approaches To Identify New Inhibitors of the Human Rhinovirus Coat Protein

Abstract

The development and application of a sophisticated virtual screening and selection protocol to identify potential, novel inhibitors of the human rhinovirus coat protein employing various computer-assisted strategies are described. A large commercially available database of compounds was screened using a highly selective, structure-based pharmacophore model generated with the program Catalyst. A docking study and a principal component analysis were carried out within the software package Cerius² and served to validate and further refine the obtained results. These combined efforts led to the selection of six candidate structures, for which in vitro antirhinoviral activity could be shown in a biological assay.