Cellular kinase pathways as a drug targeting strategy for CMV-specific or broad herpesviral intervention
Human cytomegalovirus (HCMV) is the most common infectious cause for birth defects, leading to severe pathologies such as hearing loss, microcephaly and mental retardation in newborns. Currently available anti-HCMV medication is exclusively targeted to viral proteins and hindered by side effects as well as emerging resistant virus strains. A new approach to inhibit HCMV replication has recently been postulated in antiviral compounds targeting cellular proteins instead of viral targets. Important candidates for the target protein of cell-targeted anti-HCMV drugs are cyclin-dependent kinases (CDKs), which play crucial roles in regulating the cell cycle and cellular transcription. We focus on one of these regulators, CDK7, and aim to determine its role in HCMV replication. By testing new CDK-directed antiviral compounds in cell culture and mouse models, we hope to learn more about how HCMV depends on CDKs and which compounds (or combinations thereof) are best suited to inhibit its replication.
