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Systematic Approaches towards the Development of Host-Directed Antiviral Therapeutics
Department of Chemistry, Emory University, Atlanta, GA 30322, USA
Emory Institute for Drug Discovery (EIDD), Emory University, Atlanta, GA 30322, USA
Department of Pediatrics, Emory University, Atlanta, GA 30322, USA
Children’s Healthcare of Atlanta, Atlanta, GA 30322, USA
* Authors to whom correspondence should be addressed.
Received: 27 February 2011; in revised form: 3 June 2011 / Accepted: 3 June 2011 / Published: 15 June 2011
Abstract: 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.
Keywords: genome-wide screening; pathway analysis; HIV; Influenza virus; bioinformatics; antiviral; target identification; RNAi; siRNA
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Prussia, A.; Thepchatri, P.; Snyder, J.P.; Plemper, R.K. Systematic Approaches towards the Development of Host-Directed Antiviral Therapeutics. Int. J. Mol. Sci. 2011, 12, 4027-4052.
Prussia A, Thepchatri P, Snyder JP, Plemper RK. Systematic Approaches towards the Development of Host-Directed Antiviral Therapeutics. International Journal of Molecular Sciences. 2011; 12(6):4027-4052.
Prussia, Andrew; Thepchatri, Pahk; Snyder, James P.; Plemper, Richard K. 2011. "Systematic Approaches towards the Development of Host-Directed Antiviral Therapeutics." Int. J. Mol. Sci. 12, no. 6: 4027-4052.