Focus on flaviviruses: current and future drug targets.
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.


CONCLUSIONS
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.


CONCLUSIONS
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.
Geiss
Brian J
BJ
Department of Biochemistry & Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA.
Stahla
Hillary
H
Hannah
Amanda M
AM
Gari
Amanda M
AM
Keenan
Susan M
SM
D000998:Antiviral Agents / Q000627:therapeutic use; D005416:Flavivirus / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D018177:Flavivirus Infections / Q000188:drug therapy; D006801:Humans; D054730:Protein Interaction Domains and Motifs; D020365:RNA Helicases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000998:Antiviral Agents; D020365:RNA Helicases; D012324:RNA-Dependent RNA Polymerase; D012697:Serine Endopeptidases; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C096041:NS5 protein, flavivirus