Herpesvirus helicase–primase complex

The **Herpesvirus helicase–primase complex** is a multi-protein enzyme complex essential for herpesvirus DNA replication. It typically consists of a helicase subunit (UL5 in HSV-1), a primase subunit (UL52 in HSV-1), and a non-catalytic cofactor (UL8 in HSV-1), forming a heterotrimeric complex that coordinates the unwinding of viral DNA and the synthesis of RNA primers for DNA synthesis[1][2][4][6]. The activities of helicase and primase are tightly interdependent and are only functional when both catalytic subunits are associated. The complex is evolutionarily conserved among herpesviruses, with homologous functional components in human cytomegalovirus (pUL105, pUL70, pUL102) and other family members[3]. The helicase-primase complex is a validated antiviral drug target, with several small molecule inhibitors—such as pritelivir and amenamevir—demonstrating clinical efficacy by inhibiting its ability to unwind DNA and to synthesize RNA primers, thereby blocking viral genome replication[2][7][8]. Resistance mutations have been reported in the target UL5 and UL52 genes, raising ongoing concerns about antiviral resistance[7].

Other names

HSV DNA helicase–primase complexUL5/UL8/UL52 complex (HSV-1)Helicase–primase complex (Herpesviridae)HCMV helicase–primase complex (for human cytomegalovirus variants)HP complex

Inhibition of DNA unwinding by blocking ATPase activity of the helicase subunit (UL5); Inhibition of RNA primer synthesis by interfering with primase subunit (UL52) action; Disruption of complex formation and coordination at the viral replication fork