title: Drug discovery technologies and strategies for Machupo virus and other New World arenaviruses.
abstract: BACKGROUND
  Seven arenaviruses cause viral hemorrhagic fever in humans: the Old World arenaviruses Lassa and Lujo, and the New World Clade B arenaviruses Machupo (MACV), Junín (JUNV), Guanarito (GTOV), Sabiá (SABV), and Chapare (CHPV). All of these viruses are Risk Group 4 biosafety pathogens. MACV causes human disease outbreak with high case-fatality rates. To date, at least 1,200 cases with ≈200 fatalities have been recorded.
  
  
  METHODS
  This review summarizes available systems and technologies for the identification of antivirals against MACV. Furthermore, the article summarizes animal models that have been used for the in vivo evaluation of novel inhibitors. The article highlights present treatments for arenaviral diseases and provides an overview of efficacious small molecules and other therapeutics reported to date. Finally, the article summarizes strategies to identify novel inhibitors for anti-arenaviral therapy.
  
  
  CONCLUSIONS
  New high-throughput approaches to quantitate infection rates of arenaviruses, as well as viruses modified to carry reporter genes, will accelerate compound screens and drug discovery efforts. RNAi, gene expression profiling and proteomics studies will identify host targets for therapeutic intervention. New discoveries in the cell entry mechanism of MACV and other arenaviruses as well as extensive structural studies of arenaviral L and NP could facilitate the rational design of antivirals effective against all pathogenic New World arenaviruses.
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Sheli R
authors.initials: SR
authors.lastname: Radoshitzky
authors.forename: Jens H
authors.initials: JH
authors.lastname: Kuhn
authors.forename: Fabian
authors.initials: F
authors.lastname: de Kok-Mercado
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jahrling
authors.forename: Sina
authors.initials: S
authors.lastname: Bavari
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D001117:Arenaviridae Infections / Q000188:drug therapy / Q000276:immunology; D006477:Arenaviruses, New World / Q000145:classification / Q000187:drug effects* / Q000276:immunology; D002522:Chlorocebus aethiops; D006224:Cricetinae; D055808:Drug Discovery / Q000379:methods*; D006168:Guinea Pigs; D006367:HeLa Cells; D006482:Hemorrhagic Fevers, Viral / Q000188:drug therapy; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D008253:Macaca mulatta; D051379:Mice; D034622:RNA Interference; D054852:Small Molecule Libraries / Q000378:metabolism / Q000494:pharmacology; D014765:Viral Vaccines / Q000276:immunology / Q000627:therapeutic use; D018406:Virus Physiological Phenomena
chemical_list: D000998:Antiviral Agents; D054852:Small Molecule Libraries; D014765:Viral Vaccines