Herpesvirus DNA polymerase catalytic subunit (UL30/UL54)

The Herpesvirus DNA polymerase catalytic subunit is an essential enzyme for the replication of the viral genome within the Herpesviridae family, including Herpes Simplex Virus (HSV), Varicella-Zoster Virus (VZV), and Cytomegalovirus (CMV) (UniProt P04293). It functions by catalyzing the addition of deoxynucleotides to a growing DNA strand and possesses intrinsic 3'-5' exonuclease activity for proofreading, which maintains the integrity of the viral genetic code (PubMed: 11073470). This enzyme is the primary pharmacological target for most current anti-herpetic medications, such as acyclovir and ganciclovir, which are nucleoside analogs that cause chain termination upon incorporation (StatPearls: NBK542180). Non-nucleoside inhibitors like foscarnet also target this subunit by binding to the pyrophosphate exchange site, preventing further DNA synthesis (DrugBank: DB00528). While highly effective, the clinical utility of these drugs can be limited by the development of resistance mutations within the catalytic subunit, particularly in immunocompromised patients (PubMed: 15917461).

Other names

UL30UL54BALF5U38ORF29DNA polymerase catalytic subunitDNA-directed DNA polymerase catalytic subunit

Inhibition of viral DNA synthesis through competitive inhibition of dNTP binding and/or DNA chain termination following incorporation into the nascent viral DNA strand.