title: Systematic approaches towards the development of host-directed antiviral therapeutics.
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.
authors: Department of Chemistry, Emory University, Atlanta, GA 30322, USA; E-Mails: aprussi@emory.edu (A.P.); jsnyder@emory.edu (J.P.S.).
authors: Andrew
authors: A
authors: Prussia
authors: Pahk
authors: P
authors: Thepchatri
authors: James P
authors: JP
authors: Snyder
authors: Richard K
authors: RK
authors: Plemper
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019295:Computational Biology; D016208:Databases, Factual; D015658:HIV Infections / Q000188:drug therapy; D054884:Host-Pathogen Interactions / Q000187:drug effects*; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy; D034622:RNA Interference; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents