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Int. J. Mol. Sci. 2011, 12(6), 4027-4052; doi:10.3390/ijms12064027

Systematic Approaches towards the Development of Host-Directed Antiviral Therapeutics

1
Department of Chemistry, Emory University, Atlanta, GA 30322, USA
2
Emory Institute for Drug Discovery (EIDD), Emory University, Atlanta, GA 30322, USA
3
Department of Pediatrics, Emory University, Atlanta, GA 30322, USA
4
Children’s Healthcare of Atlanta, Atlanta, GA 30322, USA
*
Authors to whom correspondence should be addressed.
Received: 27 February 2011 / Revised: 3 June 2011 / Accepted: 3 June 2011 / Published: 15 June 2011
(This article belongs to the Special Issue A Systematic Development Method for Rational Drug Design)
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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. View Full-Text
Keywords: genome-wide screening; pathway analysis; HIV; Influenza virus; bioinformatics; antiviral; target identification; RNAi; siRNA genome-wide screening; pathway analysis; HIV; Influenza virus; bioinformatics; antiviral; target identification; RNAi; siRNA
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

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.

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