Viral leads for chemokine-modulatory drugs.
The chemokine system, which controls leukocyte trafficking, provides several potentially very attractive anti-inflammatory drug targets. However, the complexity and redundancy of this system makes it very difficult to exploit through classical drug discovery. Despite this, viruses have millions of years of experience in manipulating this system. For example, virally encoded "biopharmaceuticals"--chemokines and chemokine binding proteins--demonstrate the effectiveness of blocking a carefully selected group of chemokine receptors and how the local immune response can be changed from one dominated by Th1 cells to one dominated by Th2 cells by targeting specific chemokine receptors. The crucial importance of the binding of chemokines to glycosaminoglycans to produce their effects is also highlighted by viruses that produce binding proteins to disrupt the gradient of chemokines, which guides the direction leukocyte migration.
Lindow
Morten
M
Laboratory for Molecular Pharmacology, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark.
Lüttichau
Hans Rudolf
HR
Schwartz
Thue W
TW
D000818:Animals; D001702:Biopharmaceutics / Q000379:methods*; D006801:Humans; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology; D014780:Viruses / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
D019707:Receptors, Chemokine