title: Novel approaches to flavivirus drug discovery.
abstract: BACKGROUND
  The members of the family Flaviviridae, including West Nile virus, yellow fever virus and dengue virus, are important human pathogens that are expanding their impact around the globe. The four serotypes of dengue infect 50-100 million people each year, yet the only clinical treatment is supportive care to reduce symptoms. Drugs that employ novel inhibition mechanisms and targets are urgently needed to combat the growing incidence of dengue worldwide.
  
  
  METHODS
  The authors discuss recently discovered flavivirus inhibitors with a focus on antivirals targeting non-enzymatic proteins of the dengue virus lifecycle. Specifically, the authors discuss the flaviviruses, the need for novel inhibitors and the criteria for successful antiviral drug development. Current literature describing new advances in antiviral therapy at each stage of the flavivirus lifecycle (entry, endosomal escape, viral RNA processing and replication, assembly and immune evasion) are evaluated and summarized.
  
  
  CONCLUSIONS
  Overall, the prognosis of flavivirus antiviral drug development is positive: new effective compounds have been discovered and studied. However, repurposing existing compounds and a greater translation to the clinical setting are recommended in order to combat the growing threat of flaviviruses.
authors.affiliation: Department of Biological Sciences, Bindley Bioscience Center, Purdue University, IN, USA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Botting
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Kuhn
mesh_terms: D047151:Amaryllidaceae Alkaloids / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D003716:Dengue Virus / Q000187:drug effects; D055808:Drug Discovery / Q000379:methods*; D018067:Flaviviridae / Q000187:drug effects*; D018177:Flavivirus Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D051379:Mice; D043942:Nanotubes / Q000737:chemistry; D010455:Peptides / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D012367:RNA, Viral / Q000037:antagonists & inhibitors*; D054852:Small Molecule Libraries / Q000494:pharmacology; D014759:Viral Envelope Proteins / Q000037:antagonists & inhibitors*; D014779:Virus Replication / Q000187:drug effects*; D014902:West Nile virus / Q000187:drug effects; D015005:Yellow fever virus / Q000187:drug effects
chemical_list: D047151:Amaryllidaceae Alkaloids; D000998:Antiviral Agents; D010455:Peptides; D010617:Phenanthridines; D034741:RNA, Small Interfering; D012367:RNA, Viral; D054852:Small Molecule Libraries; D014759:Viral Envelope Proteins; C015330:lycorine