Focus on flaviviruses: current and future drug targets

Future Med Chem. 2009 May;1(2):327-44. doi: 10.4155/fmc.09.27.

Abstract

Background: Infection by mosquito-borne flaviviruses (family Flaviviridae) is increasing in prevalence worldwide. The vast global, social and economic impact due to the morbidity and mortality associated with the diseases caused by these viruses necessitates therapeutic intervention. There is currently no effective clinical treatment for any flaviviral infection. Therefore, there is a great need for the identification of novel inhibitors to target the virus life cycle.

Discussion: In this article, we discuss structural and nonstructural viral proteins that are the focus of current target validation and drug discovery efforts. Both inhibition of essential enzymatic activities and disruption of necessary protein–protein interactions are considered. In addition, we address promising new targets for future research.

Conclusion: As our molecular and biochemical understanding of the flavivirus life cycle increases, the number of targets for antiviral therapeutic discovery grows and the possibility for novel drug discovery continues to strengthen.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Antiviral Agents / therapeutic use
  • Flavivirus / enzymology*
  • Flavivirus / genetics
  • Flavivirus / metabolism
  • Flavivirus Infections / drug therapy
  • Humans
  • Protein Interaction Domains and Motifs
  • RNA Helicases / antagonists & inhibitors
  • RNA Helicases / metabolism
  • RNA-Dependent RNA Polymerase / antagonists & inhibitors
  • RNA-Dependent RNA Polymerase / metabolism
  • Serine Endopeptidases / metabolism
  • Viral Envelope Proteins / antagonists & inhibitors
  • Viral Envelope Proteins / metabolism
  • Viral Nonstructural Proteins / antagonists & inhibitors
  • Viral Nonstructural Proteins / metabolism
  • Viral Proteins / antagonists & inhibitors*
  • Viral Proteins / chemistry

Substances

  • Antiviral Agents
  • NS3 protein, flavivirus
  • NS5 protein, flavivirus
  • Viral Envelope Proteins
  • Viral Nonstructural Proteins
  • Viral Proteins
  • RNA-Dependent RNA Polymerase
  • Serine Endopeptidases
  • RNA Helicases