Purification and crystallization of dengue and West Nile virus NS2B-NS3 complexes.
Both dengue and West Nile virus infections are an increasing risk to humans, not only in tropical and subtropical areas, but also in North America and parts of Europe. These viral infections are generally transmitted by mosquitoes, but may also be tick-borne. Infection usually results in mild flu-like symptoms, but can also cause encephalitis and fatalities. Approximately 2799 severe West Nile virus cases were reported this year in the United States, resulting in 102 fatalities. With this alarming increase in the number of West Nile virus infections in western countries and the fact that dengue virus already affects millions of people per year in tropical and subtropical climates, there is a real need for effective medicines. A possible therapeutic target to combat these viruses is the protease, which is essential for virus replication. In order to provide structural information to help to guide a lead identification and optimization program, crystallizations of the NS2B-NS3 protease complexes from both dengue and West Nile viruses have been initiated. Crystals that diffract to high resolution, suitable for three-dimensional structure determinations, have been obtained.
D'Arcy
Allan
A
Novartis Institutes of Biomedical Research, Protease Platform, Klybeckstrasse 144, CH 4002 Basel, Switzerland. allan.darcy@novartis.com
Chaillet
Maxime
M
Schiering
Nikolaus
N
Villard
Frederic
F
Lim
Siew Pheng
SP
Lefeuvre
Peggy
P
Erbel
Paul
P
D003460:Crystallization; D018360:Crystallography, X-Ray; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000302:isolation & purification*; D003716:Dengue Virus / Q000201:enzymology* / Q000302:isolation & purification; D006801:Humans; D046912:Multiprotein Complexes / Q000737:chemistry / Q000302:isolation & purification; D012697:Serine Endopeptidases / Q000737:chemistry / Q000302:isolation & purification*; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000302:isolation & purification*; D014902:West Nile virus / Q000201:enzymology* / Q000302:isolation & purification; D000085242:Viral Proteases
D003546:Cysteine Endopeptidases; D046912:Multiprotein Complexes; D012697:Serine Endopeptidases; D017361:Viral Nonstructural Proteins; C504449:NS3 protease, dengue virus; D000085242:Viral Proteases; C107824:NS2-3 protease