DNA primase subunit UL52 (UL52) (UL52)

The DNA primase subunit UL52 is an essential component of the heterotrimeric helicase-primase complex in Herpes Simplex Virus (HSV), which also comprises the UL5 helicase and the UL8 accessory protein (1.1.1, 1.1.2). UL52 is responsible for the synthesis of short RNA primers on the lagging strand, a process required for the initiation of DNA synthesis by the viral DNA polymerase (1.1.4, 1.2.2). It contains a conserved archaea-eukaryotic primase (AEP) domain and a zinc finger motif critical for its catalytic activity and DNA binding (1.2.3, 1.6.1). UL52 is a validated therapeutic target for helicase-primase inhibitors (HPIs) such as pritelivir and amenamevir, which offer a novel mechanism of action distinct from traditional nucleoside analogues like acyclovir (1.3.1, 1.4.1). These inhibitors bind to the helicase-primase complex, often stabilizing it on DNA to prevent replication fork progression without requiring activation by viral thymidine kinase (1.3.3, 1.4.3). Consequently, targeting UL52 is particularly effective against acyclovir-resistant HSV strains, making it a significant focus for treating refractory infections in immunocompromised patients (1.3.5, 1.6.2). The development of these inhibitors represents a major advancement in anti-herpetic therapy, addressing the clinical challenge of drug-resistant viral outbreaks (1.4.4, 1.6.2).

Other names

UL52 proteinpUL52DNA primaseHerpes simplex virus helicase-primase complex subunit UL52

Helicase-primase inhibitors (HPIs) bind to the UL5/UL52 complex, often at the DNA-binding interface or an allosteric site, to stabilize the complex on DNA and prevent the progression of the replication fork, thereby halting viral DNA synthesis (1.3.3, 1.4.1, 1.4.3).