Human cytomegalovirus protein kinase UL97 (UL97)

Human cytomegalovirus (HCMV) protein kinase UL97 is a multifunctional serine/threonine kinase essential for efficient viral replication (UniProt: P06487). It plays a critical role in the late stages of the viral life cycle, particularly in the phosphorylation of viral and host proteins to facilitate the egress of viral capsids from the nucleus (Prichard, 2009). Beyond its structural roles, UL97 is clinically significant because it is responsible for the initial phosphorylation of the antiviral prodrug ganciclovir, converting it into an active form that inhibits viral DNA polymerase (NIH: PubChem). Maribavir, a benzimidazole riboside, directly inhibits the kinase activity of UL97, thereby blocking viral maturation and exit from the host cell (FDA: Livtencity Label). Mutations in the UL97 gene, such as M460V or L595S, are the primary mechanism by which HCMV develops resistance to ganciclovir and maribavir (Chou, 2015). Consequently, UL97 is a major therapeutic target and a key biomarker for monitoring antiviral efficacy and resistance in immunocompromised patients.

Other names

pUL97HCMV UL97Serine/threonine-protein kinase UL97UL97 open reading frame

Maribavir acts as a competitive inhibitor of the UL97 protein kinase, preventing the phosphorylation of target proteins required for viral DNA synthesis and nuclear egress (FDA: Livtencity Label). Conversely, UL97 acts as a kinase that phosphorylates the prodrug ganciclovir into its active monophosphate form, which is necessary for its antiviral activity (NIH: PubChem).