Herpes simplex virus type 2 DNA polymerase (UL30) (HSV-2 Pol)

Herpes simplex virus type 2 DNA polymerase (UL30) is the essential enzyme responsible for replicating the double-stranded DNA genome of HSV-2 during its lytic phase [1, 15]. As a Family B DNA polymerase, it consists of a large catalytic subunit (UL30) that associates with a processivity factor (UL42) to perform highly efficient and faithful DNA synthesis [12, 15]. This enzyme is the primary pharmacological target for standard-of-care anti-herpetic drugs, including nucleoside analogues like acyclovir and valacyclovir, which act as chain terminators once incorporated into the viral DNA strand [11]. Pyrophosphate analogues like foscarnet also target this enzyme by blocking the pyrophosphate-binding site of the polymerase [7]. While these therapies are highly effective at controlling outbreaks and reducing viral shedding, they do not eradicate the latent virus stored in the lumbosacral ganglia [10, 18]. Clinical challenges include the development of drug-resistant strains, particularly in immunocompromised patients, which typically arise from mutations in the UL30 or thymidine kinase genes [10, 15].

Other names

Herpes simplex virus type 2 DNAHSV-2 DNA polymeraseUL30Human herpesvirus 2 DNA polymeraseDNA-directed DNA polymerase catalytic subunit (UL30)

Nucleoside analogues are phosphorylated by viral and cellular kinases to active triphosphates that competitively inhibit the viral DNA polymerase and cause premature DNA chain termination; pyrophosphate analogues non-competitively inhibit the polymerase by binding directly to the pyrophosphate-binding site [7, 11, 15].