Herpes simplex virus DNA polymerase catalytic subunit (HSV Pol)

The Herpes simplex virus DNA polymerase, specifically the catalytic subunit encoded by the UL30 gene, is the essential enzyme responsible for replicating the viral genome within host cells (UniProt: P04293). It functions as a DNA-directed DNA polymerase, synthesizing new viral DNA strands using the viral genome as a template. This enzyme is the primary therapeutic target for a class of antiviral nucleoside analogs, such as acyclovir and ganciclovir, which exhibit high selectivity for virus-infected cells (NCBI: NBK47444). These drugs are administered as prodrugs and require initial phosphorylation by the viral enzyme thymidine kinase (HSV-TK) to be converted into their active triphosphate forms. Once activated, these compounds competitively inhibit the viral DNA polymerase and, upon incorporation into the nascent DNA strand, cause premature chain termination. While highly effective, the clinical utility of targeting this enzyme can be challenged by the emergence of drug resistance, typically arising from mutations in either the UL30 polymerase gene or the UL23 thymidine kinase gene (PubMed: 11812491).

Other names

UL30DNA-directed DNA polymerase catalytic subunitHSV-1 DNA polymeraseHSV-2 DNA polymerasePol

Competitive inhibition of viral DNA polymerase and DNA chain termination following activation by viral thymidine kinase (NCBI: NBK47444).