The flavivirus protease as a target for drug discovery.
Many flaviviruses are significant human pathogens causing considerable disease burdens, including encephalitis and hemorrhagic fever, in the regions in which they are endemic. A paucity of treatments for flaviviral infections has driven interest in drug development targeting proteins essential to flavivirus replication, such as the viral protease. During viral replication, the flavivirus genome is translated as a single polyprotein precursor, which must be cleaved into individual proteins by a complex of the viral protease, NS3, and its cofactor, NS2B. Because this cleavage is an obligate step of the viral life-cycle, the flavivirus protease is an attractive target for antiviral drug development. In this review, we will survey recent drug development studies targeting the NS3 active site, as well as studies targeting an NS2B/NS3 interaction site determined from flavivirus protease crystal structures.
Wadsworth Center, New York State Department of Health, 120 New Scotland Ave, Albany, NY, 12208, USA.
Matthew
M
Brecher
Jing
J
Zhang
Hongmin
H
Li
D000998:Antiviral Agents / Q000302:isolation & purification* / Q000494:pharmacology; D055808:Drug Discovery / Q000379:methods* / Q000639:trends; D005416:Flavivirus / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D011480:Protease Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology; D020365:RNA Helicases / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000998:Antiviral Agents; D011480:Protease Inhibitors; D020365:RNA Helicases; D012697:Serine Endopeptidases; D017361:Viral Nonstructural Proteins; C080102:NS2B protein, flavivirus; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases