Systematic Approaches towards the Development of Host-Directed Antiviral Therapeutics

• Main Authors: James P. Snyder, Richard K. Plemper, Pahk Thepchatri, Andrew Prussia
• Format: Article
• Language: English
• Published: MDPI AG 2011-06-01
• Series: International Journal of Molecular Sciences
• Subjects: genome-wide screening; pathway analysis; HIV; Influenza virus; bioinformatics; antiviral; target identification; RNAi; siRNA
• Online Access: http://www.mdpi.com/1422-0067/12/6/4027/

Since the onset of antiviral therapy, viral resistance has compromised the clinical value of small-molecule drugs targeting pathogen components. As intracellular parasites, viruses complete their life cycle by hijacking a multitude of host-factors. Aiming at the latter rather than the pathogen directly, host-directed antiviral therapy has  emerged as a concept to counteract evolution of viral resistance and develop broad-spectrum drug classes. This approach is propelled by bioinformatics analysis of genome-wide screens that greatly enhance insights into the complex network of host-pathogen interactions and generate a shortlist of potential gene targets from a multitude of candidates, thus setting the stage for a new era of rational identification of drug targets for host-directed antiviral therapies. With particular emphasis on human immunodeficiency virus and influenza virus, two major human pathogens, we review screens employed to elucidate host-pathogen interactions and discuss the state of database ontology approaches applicable to defining a therapeutic endpoint. The value of this strategy for drug discovery is evaluated, and perspectives for bioinformatics-driven hit identification are outlined.