Druggableness of the Ebola Associated Genes in the Human Genome: Chemoinformatics Approaches

Abstract

The recent outbreak of the Ebola Virus Disease (EVD) urgently requires novel therapeutic approaches. While clinical trials are ongoing for an effective vaccinebased approach, a parallel effort to discover drugs is essential to provide a valuable alternative. Discovery of druggable targets for the EVD from the human proteome is a possibility. Using chemoinformatics approaches, the EVD associated proteins in the human genome can be verified rapidly for druggable structures. Using the Cancer Protein Annotation Tool from the CanSAR, a recently described 45 EVDassociated genes were analyzed for drug therapy use. Thirty-nine proteins were predicted to be druggable based on 3D structures and ligand binding potential. These proteins included a HIV associated chemokine, a coagulation factor, Heme enzyme and helicases involved in innate immune response to viruses, IFNinduced antiviral protein, an epithelial cell-specific transcriptional activator, a platelet factor and various members of the Human Killer cell immunoglobulinlike receptor family associated with fatal outcome with the Zaire variant of EVD. Ninteen of these proteins had 3D structural information available in the protein database including three enzymes. Based on ligand probability scores (>90%), three lead target proteins were identified (an enzyme, a blood factor and an epithelial cell specific transcription factor). Further, a lead drug-like compound (<1uM) was identified for the enzyme, Indoleamine 2,3-dioxygenase 1 (IDO1). A factor V antagonist was also identified in the study. The proteins described in the study offer a rationale for drug discovery approaches for EVD.