Host DNA polymerase (DNA Pol)

Host DNA polymerases are a group of essential cellular enzymes, including DNA polymerase alpha, delta, and gamma, responsible for the replication and repair of nuclear and mitochondrial DNA. In the treatment of viral infections like Cytomegalovirus (CMV), these enzymes can interact with ganciclovir triphosphate (GCV-TP), the active metabolite of the antiviral drug ganciclovir (PubChem CID 3454). Although GCV-TP is designed to selectively inhibit viral DNA polymerase, it can also act as a substrate or competitive inhibitor for host polymerases, leading to the incorporation of the analog into host DNA or the inhibition of DNA synthesis (PubMed: 2824586). This interaction is the primary cause of the drug's dose-limiting toxicities, most notably myelosuppression, which manifests as neutropenia and anemia (FDA Label: Cytovene). Furthermore, inhibition of mitochondrial DNA polymerase gamma can lead to mitochondrial dysfunction and related systemic side effects. Understanding the affinity of GCV-TP for these host enzymes is critical for optimizing therapeutic indices and managing patient safety during antiviral therapy.

Other names

Human DNA polymeraseCellular DNA polymeraseDNA-directed DNA polymeraseHost DNA-directed DNA polymerase

Competitive inhibition of deoxyguanosine triphosphate (dGTP) incorporation into DNA by host DNA polymerases, leading to slowed DNA chain elongation or termination.