title: Novel drug discovery approaches for treating arenavirus infections.
abstract: BACKGROUND
  Arenaviruses are enveloped negative stranded viruses endemic in Africa, Europe and the Americas. Several arenaviruses cause severe viral hemorrhagic fever with high mortality in humans and pose serious public health threats. So far, there are no FDA-approved vaccines and therapeutic options are restricted to the off-label use of ribavirin. The major human pathogenic arenaviruses are classified as Category A agents and require biosafety level (BSL)-4 containment.
  
  
  METHODS
  Herein, the authors cover the recent progress in the development of BSL2 surrogate systems that recapitulate the entire or specific steps of the arenavirus life cycle and are serving as powerful platforms for drug discovery. Furthermore, they highlight the identification of selected novel drugs that target individual steps of arenavirus multiplication describing their discovery, their targets, and mode of action.
  
  
  CONCLUSIONS
  The lack of effective drugs against arenaviruses is an unmatched challenge in current medical virology. Novel technologies have provided important insights into the basic biology of arenaviruses and the mechanisms underlying virus-host cell interaction. Significant progress of our understanding of how the virus invades the host cell paved the way to develop powerful novel screening platforms. Recent efforts have provided a range of promising drug candidates currently under evaluation for therapeutic intervention in vivo.
authors.affiliation: a Institute of Microbiology , University Hospital Center and University of Lausanne , Lausanne , Switzerland.
authors.forename: Antonella
authors.initials: A
authors.lastname: Pasquato
authors.affiliation: a Institute of Microbiology , University Hospital Center and University of Lausanne , Lausanne , Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kunz
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001117:Arenaviridae Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D018050:Arenavirus / Q000302:isolation & purification; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D014765:Viral Vaccines / Q000008:administration & dosage
chemical_list: D000998:Antiviral Agents; D014765:Viral Vaccines
keywords: Arenavirus; LASV; LCMV; SKI-1/S1P; antiviral; envelope glycoprotein; high throughput screening; sensor