Helicase-primase complex of herpesviruses (None universally adopted; sometimes referred to as HSV-1 UL5/UL8/UL52 complex or HCMV pUL105-pUL102-pUL70 complex, depending on viral species)

The helicase-primase complex of herpesviruses is a multifunctional enzyme complex required for viral DNA replication. In herpes simplex virus-1 (HSV-1), it consists of three proteins: UL5 (helicase), UL52 (primase), and UL8 (non-catalytic cofactor). Each component is essential for coordinated unwinding of DNA and the synthesis of RNA primers on the lagging strand, enabling viral genome propagation in infected host cells. The structure and function of this complex are conserved in other herpesviruses such as human cytomegalovirus (HCMV), where the analogous proteins are pUL105 (helicase), pUL70 (primase), and pUL102 (cofactor). The complex is the target of novel antiviral drugs (e.g., amenamevir, pritelivir) that inhibit its enzymatic activities, resulting in blockage of viral replication. Drug resistance arises through mutations in the functional domains of UL5 and UL52. The non-catalytic subunit UL8 is structurally related to the B-family of DNA polymerases but is catalytically inactive, serving a scaffold role. Therapeutic targeting of this complex is a strategy especially relevant in cases where standard polymerase inhibitors fail due to resistance.

Other names

UL5/UL8/UL52 complex (for HSV-1)pUL105-pUL102-pUL70 complex (for HCMV)Helicase–primase complex

Direct inhibition of helicase ATPase and primase activities, which disables viral DNA replication and replication fork progression. Binding of inhibitors to key motifs within the helicase/primase complex, notably within UL5 and UL52 subunits interfering with ATP binding, unwinding, and primer synthesis.