title: Baseline sensitivity of HSV-1 and HSV-2 clinical isolates and defined acyclovir-resistant strains to the helicase-primase inhibitor pritelivir.
abstract: Fifty-nine US isolates of HSV-1 and HSV-2 obtained between 1998 and 2004 were tested for sensitivity to the helicase-primase inhibitor, pritelivir (AIC316, BAY 57-1293) by plaque-reduction assay. All isolates, which were collected prior to any clinical use of primase-helicase inhibitors, were sensitive and showed mean EC50 values of 0.026 and 0.029μM for HSV-1 and HSV-2, respectively. Furthermore, several laboratory-selected acyclovir-resistant HSV mutants were also sensitive to pritelivir. These data provide a baseline for HSV sensitivity to pritelivir in general population before it is introduced and broadly used to treat HSV infection. The data also validate pritelivir as an appropriate therapy for nucleoside-resistant HSV infections.
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, United Kingdom. Electronic address: hjf10@cam.ac.uk.
authors.forename: Hugh J
authors.initials: HJ
authors.lastname: Field
authors.forename: Meei-Li
authors.initials: ML
authors.lastname: Huang
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Lay
authors.forename: Ian
authors.initials: I
authors.lastname: Mickleburgh
authors.forename: Holger
authors.initials: H
authors.lastname: Zimmermann
authors.forename: Alexander
authors.initials: A
authors.lastname: Birkmann
mesh_terms: D000212:Acyclovir / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D004265:DNA Helicases / Q000037:antagonists & inhibitors*; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000302:isolation & purification; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008826:Microbial Sensitivity Tests; D011725:Pyridines / Q000494:pharmacology*; D013449:Sulfonamides; D013844:Thiazoles / Q000494:pharmacology*; D014481:United States; D010948:Viral Plaque Assay
chemical_list: D000998:Antiviral Agents; D011725:Pyridines; D013449:Sulfonamides; D013844:Thiazoles; C453221:pritelivir; D004265:DNA Helicases; D000212:Acyclovir
keywords: AIC316; BAY 57-1293; HSV; Helicase–primase; Pritelivir