Herpes simplex virus DNA polymerase (HSV DNA polymerase) (HSV DNA polymerase)

The Herpes simplex virus (HSV) DNA polymerase is a heterodimeric enzyme complex essential for the replication of the viral genome (UniProt P04293). It consists of the UL30 catalytic subunit, which possesses both 5'-3' DNA polymerase and 3'-5' exonuclease activities, and the UL42 processivity factor that stabilizes the polymerase on the DNA template (PubMed: 11831707). This complex is a central component of the viral replication machinery, which also includes the helicase-primase complex (StatPearls: NBK482332). As a primary therapeutic target, the polymerase is inhibited by nucleoside analogs like acyclovir, which act as obligate chain terminators during DNA synthesis (PubChem CID 135398508). Non-nucleoside inhibitors, such as foscarnet, target the pyrophosphate-binding site of the enzyme to block nucleotide incorporation (NIH: LiverTox). Resistance typically emerges through mutations in the UL30 gene or the viral thymidine kinase, posing challenges in immunocompromised patients (PubMed: 25534376). Newer agents like pritelivir target the helicase-primase component of the replication machinery, providing an alternative for resistant strains (PubMed: 24428469). The enzyme's high selectivity for viral over host DNA synthesis makes it an ideal target for antiviral drug development. Clinical monitoring often involves measuring viral load and sequencing the UL30/UL23 genes to detect resistance-associated mutations. Overall, the HSV DNA polymerase remains the most successful target for managing herpesvirus infections globally.

Other names

UL30UL42DNA-directed DNA polymeraseHSV replication complexHelicase-primase complexEarly-stage replication machinery

Competitive inhibition of viral DNA polymerase and obligate DNA chain termination