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Int J Mol Sci. 2011;12(6):4027-52. doi: 10.3390/ijms12064027. Epub 2011 Jun 15.

Systematic approaches towards the development of host-directed antiviral therapeutics.

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Department of Chemistry, Emory University, Atlanta, GA 30322, USA; E-Mails: (A.P.); (J.P.S.).


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.


HIV; Influenza virus; RNAi; antiviral; bioinformatics; genome-wide screening; pathway analysis; siRNA; target identification

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