Lipid kinase inhibitors as potential therapeutics

Phosphatidylinositol 4-kinases (PI4Ks) catalyze a transfer of phosphates from ATP to phosphatidylinositoles, common constituents of cellular membranes. The product of this reaction is phosphatidylinositol 4-phosphate (PI4P), which plays a crucial role in a number of cellular processes - especially endocytosis, secretion and signaling. Human cell contains four different PI4Ks classified into two classes - class II comprising PI4K IIα and PI4K IIβ and class III with PI4K IIIα and PI4K IIIβ.

The class III PI4Ks have recently been implicated in the replication of numerous (+)ssRNA viruses including members of the Picornaviridae, Coronaviridae and Flaviviridae family. One of our major projects focuses on the design and synthesis of novel PI4K IIIβ inhibitors. Recently, we prepared a novel series of compounds highly selective towards this isoenzyme, which does not affect the other PI4Ks and PI3Ks. Our work continues by the exploration of structure-activity relationship of these compounds and investigation of novel inhibitors of other PI4Ks.

Novel heterocyclic derivatives as antiviral compounds

A part of our work is also focused on structure-based design of novel heterocyclic compounds active against various viral infections. Among others we have been dealing with synthesis of compounds against HIV, Hepatitis B and C and tick-born encephalitis. In this research field, we have been mostly interested in nucleoside and nucleotide analogues and their prodrugs.