Human cytomegalovirus UL97 protein kinase (UL97) (UL97)

The Human cytomegalovirus (HCMV) UL97 protein kinase, also known as pUL97, is a viral serine/threonine kinase that functions as an ortholog of host cyclin-dependent kinases (vCDK) (MDPI, 2015). It plays a critical role in the HCMV life cycle by phosphorylating both viral and cellular substrates to facilitate viral DNA replication, virion morphogenesis, and the egress of mature nucleocapsids from the host cell nucleus (UniProt P16788). Beyond its endogenous roles, UL97 is clinically significant as the enzyme responsible for the initial monophosphorylation of the antiviral prodrug ganciclovir, a step essential for its conversion into an active DNA polymerase inhibitor (Nature, 1992). Consequently, mutations in the UL97 gene are the primary cause of clinical resistance to ganciclovir and its prodrug valganciclovir (NIH, 2025). Maribavir is a potent and selective inhibitor of UL97 that works by competitively binding to its ATP-binding site, thereby disrupting multiple stages of viral replication (NIH, 2024). While maribavir offers a therapeutic option for refractory or resistant HCMV infections, its use is associated with safety concerns such as dysgeusia and the potential for developing further resistance mutations within the UL97 kinase domain (FDA, 2021).

Other names

pUL97UL97 kinaseSerine/threonine-protein kinase UL97Ganciclovir kinaseHCMV UL97

Maribavir acts as a competitive inhibitor of the UL97 kinase at the ATP-binding site, preventing the phosphorylation of substrates required for viral egress and DNA replication (NIH, 2024). Conversely, UL97 serves as a phosphotransferase that activates ganciclovir and valganciclovir by performing the initial monophosphorylation step necessary for their antiviral activity (Nature, 1992).