Herpes simplex virus 2 DNA polymerase (HSV-2 DNA polymerase)

Herpes simplex virus 2 DNA polymerase (UL30 gene product) is a large, multifunctional viral enzyme belonging to the B family of DNA polymerases. It is essential for catalyzing replication of the HSV-2 viral genome during lytic infection. This polymerase operates in conjunction with a processivity factor (UL42) to ensure efficient DNA synthesis. It has intrinsic 3′–5′ exonuclease (proofreading) activity, contributing to replication fidelity, and its structure and function closely resemble those of HSV-1 DNA polymerase. This enzyme is the principal target for widely used antiviral drugs, particularly nucleoside analogues such as acyclovir, which act by causing chain termination. Drug resistance can occur due to mutations in the polymerase gene, necessitating alternative therapies in refractory cases. HSV polymerase inhibitors generally demonstrate a high degree of viral selectivity, resulting in a favorable safety profile, though vigilance for resistance emergence is clinically important.

Other names

HSV-2 UL30 (gene name/product)HSV-2 DNA PolHerpesvirus DNA polymeraseViral DNA polymerase (herpesvirus-specific)

Nucleoside analogues: Incorporated into viral DNA by the polymerase, resulting in chain termination due to lack of a 3′-OH group (e.g., acyclovir, penciclovir). Pyrophosphate analogues (foscarnet): Bind to the pyrophosphate binding site, inhibiting nucleotide addition. Non-nucleoside inhibitors: Bind to the active site, induce conformational changes, and block catalytically competent DNA synthesis. Resistance mutations: May alter active site to reduce drug binding.