title: Superior efficacy of helicase-primase inhibitor BAY 57-1293 for herpes infection and latency in the guinea pig model of human genital herpes disease.
abstract: The efficacy of BAY 57-1293, a novel non-nucleosidic inhibitor of herpes simplex virus 1 and 2 (HSV-1 and HSV-2), bovine herpesvirus and pseudorabies virus, was studied in the guinea pig model of genital herpes in comparison with the licensed drug valaciclovir (Valtrex). Early therapy with BAY 57-1293 almost completely suppressed the symptoms of acute HSV-2 infection, and reduced virus shedding and viral load in the sacral dorsal root ganglia by up to three orders of magnitude, resulting in decreased latency and a greatly diminished frequency of subsequent recurrent episodes. In contrast, valaciclovir showed only moderate effects in this set of experiments. When treatment was initiated late during the course of disease after symptoms were apparent, that is, a setting closer to most clinical situations, the efficacy of therapy with BAY 57-1293 was even more pronounced. Compared with valaciclovir, BAY 57-1293 halved the time necessary for complete healing. Moreover, the onset of action was fast, so that only very few animals developed new lesions after treatment commenced. Finally, in a study addressing the treatment of recurrent disease in animals whose primary infection had remained untreated BAY 57-1293 was efficient in suppressing the episodes. In summary, superior potency and efficacy of BAY 57-1293 over standard treatment with valaciclovir was demonstrated in relevant animal models of human genital herpes disease in terms of abrogating an HSV infection, reducing latency and the frequency of subsequent recurrences. Furthermore, BAY 57-1293 shortens the time to healing even if initiation of therapy is delayed.
authors.affiliation: AiCuris GmbH & Co KG, Wuppertal, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Baumeister
authors.forename: Ruediger
authors.initials: R
authors.lastname: Fischer
authors.forename: Peter
authors.initials: P
authors.lastname: Eckenberg
authors.forename: Kerstin
authors.initials: K
authors.lastname: Henninger
authors.forename: Helga
authors.initials: H
authors.lastname: Ruebsamen-Waigmann
authors.forename: Gerald
authors.initials: G
authors.lastname: Kleymann
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004265:DNA Helicases / Q000037:antagonists & inhibitors*; D019915:DNA Primase / Q000037:antagonists & inhibitors*; D004279:DNA, Viral / Q000235:genetics; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000188:drug therapy*; D018258:Herpesvirus 2, Human / Q000235:genetics; D006801:Humans; D016133:Polymerase Chain Reaction; D011725:Pyridines / Q000494:pharmacology* / Q000627:therapeutic use; D013449:Sulfonamides; D013844:Thiazoles / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D004791:Enzyme Inhibitors; D011725:Pyridines; D013449:Sulfonamides; D013844:Thiazoles; C453221:pritelivir; D019915:DNA Primase; D004265:DNA Helicases