Structural targeting of PI4 kinases

Phosphatidylinositol phosphates (PIPs) are universal markers of intracellular membranes. Phosphatidylinositol 4-phosphate (PI4P) is the single most abundant mono phosphoinositide that defines the membranes of the Golgi and TGN. It has been reported to play a key role in membrane biogenesis, vesicular transport, lipid dynamics, and protein and lipid sorting in the TGN. Importantly, the replication of several RNA viruses, mainly the Hepatitis C virus (HCV), depends on PI(4)P. The goal of this project is to develop highly specific inhibitors of PI4Ks that could be used as antiviral agents. Recently, we have solved the crystal structure of PI4K II alpha and III beta with ATP and with an inhibitor. The structures explain how these inhibitors work and they are guiding us towards more specific and potent drugs.