Herpes simplex virus type 1 helicase-primase complex (HSV-1 H-P complex)

The Herpes simplex virus type 1 (HSV-1) helicase-primase complex is a vital heterotrimeric enzyme system essential for the replication of the viral genome. It consists of three subunits: UL5, which provides 5'-3' helicase activity; UL52, which possesses primase and DNA-dependent RNA polymerase activities; and UL8, which acts as a scaffold to facilitate complex assembly and nuclear localization (Source: UniProt P10236, P10239, P10235). During replication, the complex unwinds the DNA duplex and synthesizes RNA primers necessary for lagging-strand synthesis. As a therapeutic target, it is particularly significant because it does not require activation by viral thymidine kinase, making it a potent target for treating acyclovir-resistant HSV-1 infections (Source: PubMed PMID 24428469). Current drug candidates like Pritelivir target this complex to inhibit viral shedding and lesion formation in both immunocompetent and immunocompromised patients (Source: NEJM 2014; 370:201-210).

Other names

UL5/UL8/UL52 complexHSV-1 helicase-primaseHerpes simplex virus 1 helicase-primaseHSV-1 DNA helicase-primase

Helicase-primase inhibitors (HPIs) bind directly to the complex and stabilize the enzyme-DNA interaction, which prevents the progression of the replication fork and inhibits viral DNA synthesis without requiring phosphorylation by viral kinases (Source: PubMed PMID 11927949, 24428469).