Herpes simplex virus helicase subunit UL5 (UL5) (UL5)

The UL5 helicase subunit is an essential component of the heterotrimeric helicase-primase complex in Herpes Simplex Virus (HSV), which also includes the UL52 primase and UL8 scaffold subunits (UniProt P04290). UL5 functions as a DNA-dependent ATPase and ATP-dependent 5'-3' DNA helicase, providing the mechanical force required to unwind double-stranded DNA at the replication fork (PubMed: 11961546). This complex is a validated therapeutic target for a class of antiviral drugs known as helicase-primase inhibitors (HPIs), such as pritelivir and amenamevir (PubMed: 24428469). Unlike traditional nucleoside analogs like acyclovir, HPIs do not require phosphorylation by viral thymidine kinase to be active, making them effective against acyclovir-resistant HSV strains (PubMed: 28242756). By binding to the helicase-primase complex, these drugs prevent the unwinding of the viral genome and the initiation of DNA synthesis, thereby inhibiting viral replication and reducing clinical symptoms. UL5 is particularly significant in drug development because many resistance-conferring mutations map directly to its highly conserved helicase motifs (PubMed: 15939900).

Other names

UL5 proteinHSV-1 UL5HSV-2 UL5DNA helicase UL5UL5 helicase-primase subunit

Inhibition of the viral helicase-primase complex, preventing DNA unwinding and primer synthesis during viral replication.