Herpesvirus DNA-directed DNA polymerase (DNA pol)

Herpesvirus DNA-directed DNA polymerase is a central enzyme in the life cycle of herpesviruses, including Herpes Simplex Virus (HSV) and Varicella-Zoster Virus (VZV), where it facilitates the replication of the viral double-stranded DNA genome (Source: UniProt P04293). This enzyme is a member of the Type-B DNA polymerase family and is essential for viral proliferation, making it a premier target for antiviral therapy (Source: PubMed PMC3519134). Drugs like acyclovir and sorivudine are nucleoside analogs that function as prodrugs; they are selectively phosphorylated by viral thymidine kinase into monophosphates and subsequently by cellular kinases into active triphosphate forms, such as acyclovir-TP and sorivudine-TP (Source: StatPearls, "Acyclovir"). These triphosphates act as competitive inhibitors of natural dNTPs (dGTP for acyclovir and dTTP for sorivudine) and are incorporated into the nascent DNA chain, leading to chain termination or stalled elongation (Source: PubChem CID 135398513). The high selectivity of these drugs arises from the viral polymerase's significantly higher affinity for the analogs compared to host cellular DNA polymerases (Source: NIH LiverTox). However, clinical challenges include the emergence of resistant viral strains through mutations in the polymerase gene (UL30) and severe drug-drug interactions, most notably the lethal interaction between sorivudine and 5-fluorouracil due to the inhibition of dihydropyrimidine dehydrogenase (Source: PubMed PMID 8202753).

Other names

UL30BALF5UL54DNA-directed DNA polymeraseViral DNA polymeraseHerpesvirus DNA polymerase

Competitive inhibition of viral DNA polymerase and DNA chain termination (Source: StatPearls).