Systematic Approaches towards the Development of Host-Directed Antiviral Therapeutics

International Journal of Molecular Sciences

Andrew Prussia¹  Pahk Thepchatri¹  James P. Snyder¹ 

[1] Department of Chemistry, Emory University, Atlanta, GA 30322, USA; E-Mails:

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

DOI  :  10.3390/ijms12064027

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2011 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.