Project
A basic research pipeline for discovery and early preclinical development of host-targeted antiviral strategies to combat encephalitic alphaviruses
Within the consortium, selective GAK, selective AAK1, as well as dual GAK/AAK1 inhibitors, are
available that demonstrate already great promise against encephalitic alphaviruses. The Laboratory
of Medicinal Chemistry is responsible for the optimisation of these lead AAK1 and GAK inhibitors. A
main focus of this optimisation campaign is the improvement of the antiviral activity. Kinase
selectivity, physicochemical properties (such as metabolic stability, cellular permeability and aqueous
solubility) as well as blood-brain barrier permeation are also important properties that will be taken
into account and will be experimentally assessed in the course of the project. From a medicinal
chemistry standpoint of view, the major strategy will be to introduce variation of the substitution
pattern, although for selected compounds also scaffold hopping will be applied.