DNA polymerase of herpesvirus

DNA polymerase of herpesvirus is a **viral enzyme essential for replication of the double-stranded DNA genomes** of herpesviruses, including herpes simplex virus (HSV) and human cytomegalovirus (HCMV). It is a **member of the B family of DNA polymerases**, often forming a **complex with a processivity factor** (UL42 for HSV-1) that enhances its ability to synthesize long stretches of DNA. The enzyme exhibits **both polymerase activity, catalyzing DNA chain elongation, and 3′–5′ exonuclease proofreading activity for error correction** during replication[1][2][4][7]. DNA polymerase is the primary target for current anti-herpesvirus drugs, particularly the nucleoside analogues and pyrophosphate analogues. Clinically relevant drug resistance can emerge primarily via mutations in the polymerase gene, posing therapeutic challenges, especially in immunocompromised hosts[4][3][6]. The structure and dynamics of the DNA polymerase–DNA–inhibitor complexes have provided insight into mechanisms of action and resistance, supporting ongoing antiviral drug development and refinement[1][2][7].

Other names

Herpesvirus DNA polymeraseHSV DNA polymeraseHSV-1 polymeraseUL30 polymerase (specifically for herpes simplex virus 1)Human herpesvirus DNA polymerase

Nucleoside analogues: Incorporated into viral DNA by the polymerase, leading to chain termination and inhibition of viral DNA synthesis (e.g., acyclovir, valacyclovir, penciclovir, ganciclovir)[6][3][4]. Pyrophosphate analogues: Bind the pyrophosphate binding site, blocking DNA elongation (e.g., foscarnet)[6]. Non-nucleoside inhibitors: Bind the polymerase active site or alter its conformation to inhibit polymerase activity (e.g., PNU-183792)[7].