Herpes simplex virus DNA helicase–primase complex

The **Herpes simplex virus DNA helicase–primase complex** is a critical heterotrimeric protein complex involved in the replication of HSV-1 and HSV-2 genomes. It is composed of three viral proteins: **UL5** (the helicase), **UL52** (the primase), and **UL8** (a non-catalytic regulatory subunit)[3][5][6]. The complex is responsible for unwinding duplex viral DNA and synthesizing short RNA primers needed by the viral DNA polymerase for the initiation of DNA synthesis[3][7]. The UL5 helicase hydrolyzes ATP to translocate along and unwind the DNA, while the UL52 primase synthesizes RNA primers on the exposed single-stranded DNA. UL8 acts to coordinate and stabilize the enzymatic activities of UL5 and UL52 at the replication fork[3][5][7]. Given its essential role in HSV DNA replication and absence in host (human) DNA replication machinery, it is a validated **therapeutic target** for HSV infection and the focus of drug development efforts, especially given resistance to standard nucleoside analogues (e.g., acyclovir)[2][3][4][6][8]. Several classes of small-molecule inhibitors—**helicase–primase inhibitors** (HPIs)—have demonstrated potent antiviral activity, with some progressing to advanced clinical development. These agents offer alternatives for patients with drug-resistant HSV and potentially broader spectrum activity against other herpesviruses[2][4][6][8]. No routine biomarkers specific to helicase–primase complex inhibition are currently used in clinical practice. Safety concerns, including the risk of resistance and off-target toxicity, remain to be fully elucidated for all investigational agents in this class[4][6][8].

Other names

HSV helicase–primaseHSV-1 helicase–primase complexUL5/UL8/UL52 complex

Inhibition of helicase activity; Inhibition of primase activity; Inhibition of viral DNA replication by blocking ATPase or nucleic acid binding functions