Herpes simplex virus type 1 DNA polymerase (UL30) (UL30)

The Herpes simplex virus type 1 DNA polymerase is a vital enzyme responsible for the replication of the HSV-1 double-stranded DNA genome [1, 17]. Encoded by the UL30 gene, it serves as the catalytic subunit of the viral replisome and functions as a heterodimer with its processivity factor, UL42 [11, 13]. This enzyme belongs to the Family B DNA polymerases and exhibits multiple catalytic activities, including 5'-3' DNA polymerization, 3'-5' proofreading exonuclease, and RNase H activity [17, 21]. In clinical practice, it is the primary target for most anti-herpetic therapies, including nucleoside analogs like acyclovir and pyrophosphate analogs like foscarnet [1, 4]. These drugs inhibit viral replication by either causing premature DNA chain termination or by blocking the enzyme's active site [5, 20]. Despite the efficacy of these treatments, the emergence of drug-resistant strains—often due to mutations in the UL30 gene—poses a significant challenge, particularly in immunocompromised patients [16, 17]. Understanding the structural dynamics of this polymerase is essential for developing next-generation antivirals that can overcome existing resistance mechanisms [4, 12].

Other names

UL30DNA-directed DNA polymerase catalytic subunitPolHSV-1 PolHSV-1 DNA pol

Competitive inhibition of viral DNA polymerase and DNA chain termination (nucleoside/nucleotide analogs); direct inhibition of the pyrophosphate binding site (pyrophosphate analogs).