Structural highlights
Function
HELI_HHV11 Component of the helicase/primase complex. Unwinds the DNA at the replication forks and generates single-stranded DNA for both leading and lagging strand synthesis. The primase synthesizes short RNA primers on the lagging strand that the polymerase elongates using dNTPs. Possesses helicase-like motifs and therefore may act as the helicase subunit of the complex.[HAMAP-Rule:MF_04030]
Publication Abstract from PubMed
Widespread herpesvirus infections are associated with various diseases. DNA replication of human herpes simplex virus type 1 (HSV-1) requires a helicase-primase (HP) complex of three core proteins: UL5, UL52, and UL8. This complex unwinds viral DNA and synthesizes primers for DNA replication, making it an attractive antiviral target. Although HP inhibitors pritelivir and amenamevir were identified through screening, their binding mechanisms remain unclear. Here, we report cryo-electron microscopy structures of HSV-1 HP bound to a forked DNA template alone and in complex with pritelivir or amenamevir. The structures reveal a bilobed architecture highlighting HP coordinated action at the replication fork and providing a structural basis for HP inhibition by illustrating precisely how pritelivir and amenamevir block helicase activity. Data lay a solid foundation for the development of improved antiviral therapies.
Structural basis of herpesvirus helicase-primase inhibition by pritelivir and amenamevir.,Baranovskiy AG, He Q, Suwa Y, Morstadt LM, Babayeva ND, Lim CJ, Tahirov TH Sci Adv. 2025 Nov 7;11(45):eadz1989. doi: 10.1126/sciadv.adz1989. Epub 2025 Nov , 7. PMID:41202142[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Baranovskiy AG, He Q, Suwa Y, Morstadt LM, Babayeva ND, Lim CJ, Tahirov TH. Structural basis of herpesvirus helicase-primase inhibition by pritelivir and amenamevir. Sci Adv. 2025 Nov 7;11(45):eadz1989. PMID:41202142 doi:10.1126/sciadv.adz1989
