Proteomic and phosphoproteomic analysis of rabies pathogenesis in the clinical canine brain and identification of a kinase inhibitor as a potential repurposed antiviral agent

The kinases involved in the phosphorylation of proteins in the synaptic vesicle cycle were identified and examined as potential drug targets. Casein kinase 2 and protein kinase C were found to be key kinases for RABV replication, and five inhibitors of these enzymes were tested for their anti-RABV properties. Pretreating cells with the kinase inhibitor sunitinib significantly reduced the viral yield after RABV infection.

Our findings suggest that RABV interferes with synaptic communication, which leads to rabies, and that inhibiting a vital kinase can reduce viral production. Hence, our findings have implications for the development of rabies treatment regimes.