DNA polymerase catalytic subunit (viral, e.g., human cytomegalovirus DNA polymerase)

The target as stated, "DNA polymerase in dividing cells exposed to phosphorylated ganciclovir," is imprecise. The therapeutically relevant target of phosphorylated ganciclovir is the **viral DNA polymerase** (especially from herpesviruses such as cytomegalovirus), not the host cell's own DNA polymerases. Ganciclovir triphosphate inhibits viral DNA polymerases much more potently than cellular ones[1][2][4]. Thus, the correct canonical form should specify "Viral DNA polymerase" or "Cytomegalovirus DNA polymerase." The **viral DNA polymerase** is an essential enzyme encoded by herpesviruses such as human cytomegalovirus. It catalyzes the replication of viral genomic material during infection. Phosphorylated ganciclovir acts as a nucleoside analog that selectively inhibits this enzyme by being incorporated into nascent viral DNAs, causing premature chain termination and halting further replication. This selectivity arises because phosphorylation to its active form occurs predominantly in virus-infected cells due to expression of virus-specific kinases; thus, antiviral activity is achieved with minimal impact on host cellular enzymes at therapeutic doses[1][2][3][4]. Resistance can develop through mutations in the exonuclease domain or catalytic site of the viral enzyme[3]. “Ganciclovir’s antiviral activity inhibits virus replication...the drug must be converted to the active form by a virus‐encoded cellular enzyme...In vitro, ganciclovir triphosphate stops replication of herpes viral DNA...Ganciclovir inhibits viral DNA polymerases more effectively than it does cellular polymerases...” [1] “The primary mechanism ... is inhibition ... by ganciclovir‐5′‐triphosphate ... includes a selective and potent inhibition of the viral DNA polymerase.” [4]

Other names

Viral DNA polymeraseCytomegalovirus (CMV) DNA polymeraseHerpesvirus DNA-dependent DNA polymerase

Inhibition of viral DNA synthesis by competitive inhibition and chain termination after incorporation of drug triphosphate into viral nucleic acids[1][2][3][4].