title: Potential chemotherapeutic targets for Japanese encephalitis: current status of antiviral drug development and future challenges.
abstract: BACKGROUND
  Japanese encephalitis (JE) remains a public health threat in Asia. Although several vaccines have been licensed, ∼ 67,900 cases of the disease are estimated to occur annually, probably because the vaccine coverage is low. Therefore, effective antiviral drugs are required to control JE. However, no licensed anti-JE drugs are available, despite extensive efforts to develop them.
  
  
  METHODS
  We provide a general overview of JE and JE virus, including its transmission cycle, distribution, structure, replication machinery, immune evasion mechanisms and vaccines. The current situation in antiviral drug development is then reviewed and future perspectives are discussed.
  
  
  CONCLUSIONS
  Although the development of effective anti-JE drugs is an urgent issue, only supportive care is currently available. Recent progress in our understanding of the viral replication machinery and immune evasion strategies has identified new targets for anti-JE drug development. To date, most candidate drugs have only been evaluated in single-drug formulations, and efficient drug delivery to the CNS has virtually not been considered. However, an effective anti-JE treatment is expected to be achieved with multiple-drug formulations and a targeted drug delivery system in the near future.
authors.affiliation: a 1 Dokkyo Medical University, School of Medicine, Department of Microbiology , 880 Kitakobayashi, Mibu-machi, Shimotsuga-gun, Tochigi 321-0293, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: b 2 Mahidol University, BIKEN Endowed Department of Dengue Vaccine Development, Faculty of Tropical Medicine , 420/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand.|c 3 Osaka University, Research Institute for Microbial Diseases, BIKEN Endowed Department of Dengue Vaccine Development , 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan +66 2 354 5981 ; ekon@biken.osaka-u.ac.jp.
authors.forename: Eiji
authors.initials: E
authors.lastname: Konishi
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D016503:Drug Delivery Systems; D015195:Drug Design; D004664:Encephalitis Virus, Japanese / Q000302:isolation & purification; D004672:Encephalitis, Japanese / Q000188:drug therapy* / Q000517:prevention & control / Q000821:virology; D006801:Humans; D022321:Japanese Encephalitis Vaccines / Q000008:administration & dosage; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D022321:Japanese Encephalitis Vaccines
keywords: Japanese encephalitis; antiviral; broad spectrum; central nervous system; in silico modeling; nucleic acid-based; virus replication cycle-based