Herpes simplex virus helicase-primase subunit UL8 (UL8) (UL8)

Herpes simplex virus helicase-primase subunit UL8 is an essential component of the heterotrimeric helicase-primase complex, which also includes the UL5 helicase and UL52 primase subunits [1, 8]. While UL8 lacks independent catalytic activity, it serves as a critical scaffold protein that coordinates the activities of the other subunits, facilitates the nuclear localization of the primase subunit, and ensures efficient primer utilization during viral DNA replication [10, 14, 20]. This complex is responsible for unwinding double-stranded viral DNA and synthesizing RNA primers, making it a vital target for novel antiviral therapies [3, 11]. Drugs such as pritelivir and amenamevir act as helicase-primase inhibitors (HPIs) by binding to the complex and stabilizing its interaction with DNA, effectively halting the replication fork [4, 11, 22]. These inhibitors are particularly valuable for treating acyclovir-resistant strains of HSV-1 and HSV-2, as they target a different stage of the viral life cycle than traditional nucleoside analogues [7, 12, 17]. Clinical development of these agents focuses on immunocompromised patients and those with refractory infections, offering a potent alternative to standard-of-care treatments [12, 16, 23].

Other names

UL8 proteinHelicase-primase complex subunit UL8Primase-associated factorDNA helicase/primase complex-associated protein

Inhibition of the viral helicase-primase complex (UL5/UL8/UL52), which prevents the unwinding of double-stranded DNA and the synthesis of RNA primers required for viral DNA replication.