Herpes simplex virus helicase-primase subunit UL5 (UL5)

Herpes simplex virus helicase-primase subunit UL5 is an essential enzymatic component of the heterotrimeric helicase-primase complex (UL5/UL8/UL52) required for viral DNA replication (UniProt P04292). As a member of the Superfamily 1 (SF1) helicases, UL5 contains seven conserved motifs that facilitate ATP- or GTP-driven unwinding of double-stranded DNA in a 5' to 3' direction at the replication fork (PubMed 1561924). It works in close coordination with the UL52 primase subunit, which synthesizes RNA primers, and the UL8 scaffold protein, which coordinates the complex's activities and facilitates nuclear localization (PubMed 21613589). UL5 is a primary target for a novel class of non-nucleoside antivirals known as helicase-primase inhibitors (HPIs), including pritelivir and amenamevir (PubMed 34353927). These drugs bind to the UL5 subunit to inhibit DNA unwinding and primer synthesis, effectively halting viral genome duplication. Because HPIs do not require activation by viral thymidine kinase, they remain potent against acyclovir-resistant strains, making UL5 a critical target for treating refractory herpes simplex and varicella-zoster virus infections (PubMed 28838958).

Other names

UL5Helicase-primase helicase subunitDNA helicase-primase complex subunit UL5HSV-1 UL5HSV-2 UL5

Helicase-primase inhibition