DNA-directed DNA polymerase (UL54) (UL54)

DNA-directed DNA polymerase (UL54) is an essential enzyme for the replication of Human Cytomegalovirus (HCMV), a member of the Herpesviridae family. It catalyzes the synthesis of viral DNA by incorporating deoxynucleoside triphosphates into the growing DNA strand [UniProt: P06479]. This enzyme is the primary pharmacological target for ganciclovir and its orally bioavailable prodrug, valganciclovir [StatPearls: NBK554403]. Upon entering an infected cell, ganciclovir is converted to its active triphosphate form, which then acts as a competitive inhibitor of deoxyguanosine triphosphate (dGTP) [PubChem: CID 3454]. The incorporation of ganciclovir triphosphate into the viral DNA chain results in the cessation of DNA elongation, effectively inhibiting viral proliferation [FDA: Valcyte Label]. Clinical resistance to these therapies often arises from specific mutations within the UL54 polymerase gene or the UL97 kinase gene, which is responsible for the initial phosphorylation of the drug [PubMed: 11585538]. Targeting this enzyme is crucial for managing CMV infections in immunocompromised patients, such as those with HIV/AIDS or organ transplant recipients.

Other names

HCMV DNA polymeraseHuman cytomegalovirus DNA polymeraseUL54 gene productPol

Competitive inhibition of deoxyguanosine triphosphate (dGTP) incorporation into viral DNA by the active triphosphate form of the drug, resulting in DNA chain termination [StatPearls: NBK554403].