Discovery of a Baloxavir-Inspired Endonuclease Inhibitor That Prevents Herpes Simplex Virus 1 Replication in Cell Culture and In Vivo.

ABSTRACT: Herpes simplex viruses (HSV-1 and HSV-2) are highly prevalent and contagious, causing lifelong infections that cannot be eradicated with current therapies. Acyclovir and other viral DNA polymerase inhibitors are effective antiviral agents for treating HSV infections. However, despite the recent approval of pritelivir and amenamevir (helicase-primase complex inhibitors), drug resistance is still a major threat to therapeutic success. This research focuses on developing new antiviral strategies against HSV-1 by targeting the pUL15 endonuclease, a component of the viral packaging motor/terminase complex, using substituted polycyclic pyridones derived from baloxavir acid. Several compounds display low micromolar IC₅₀ values in enzymatic assays. Among them, the prioritized compound,

SUBMITTER: Andreu S 

PROVIDER: S-EPMC12622528 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature