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Helicase-primase inhibitors for the treatment of herpes simplex virus infections - patent evaluation of WO2023/225162 from Gilead Sciences Inc.
Expert Opin Ther Pat
October 2024
Innovative Molecules GmbH, München, Germany.
Helicase-primase is an interesting target for small-molecule therapy of herpes simplex virus (HSV) infections. With amenamevir already approved for varicella-zoster virus and herpes simplex in Japan and with 's granted breakthrough therapy designation for the treatment of acyclovir-resistant HSV infections in immunocompromised patients, the target has sparked interest in helicase-primase inhibitors (HPIs). Here, we analyze the first patent application from Gilead in this field, which pursued a me-too approach combining elements from an old Bayer together with a recent Medshine HPI application (which covers the Phaeno Therapeutics drug candidate ).
View Article and Find Full Text PDFDiscovery, Chemistry, and Preclinical Development of Pritelivir, a Novel Treatment Option for Acyclovir-Resistant Herpes Simplex Virus Infections.
J Med Chem
October 2022
AiCuris Anti-Infective Cures AG, 42117 Wuppertal, Germany.
When the nucleoside analogue acyclovir was introduced in the early 1980s, it presented a game-changing treatment modality for herpes simplex virus infections. Since then, work has been ongoing to improve the weaknesses that have now been identified: a narrow time window for therapeutic success, resistance in immunocompromised patients, little influence on frequency of recurrences, relatively fast elimination, and poor bioavailability. The present Drug Annotation focuses on the helicase-primase inhibitor pritelivir currently in development for the treatment of acyclovir-resistant HSV infections and describes how a change of the molecular target (from viral DNA polymerase to the HSV helicase-primase complex) afforded improvement of the shortcomings of nucleoside analogs.
View Article and Find Full Text PDFPritelivir for recurrent aciclovir-resistant herpes simplex virus 2 infections in immunocompromised patients.
J Antimicrob Chemother
July 2022
Laboratoire de microbiologie clinique, Hôpital Necker - Enfants malades, Groupe hospitalo-universitaire APHP Centre - Université Paris Cité, Paris, France.
Use of pritelivir in refractory aciclovir-resistant herpes simplex virus type 2.
Int J STD AIDS
September 2021
Northern Sexual Health, 8943Contraception and HIV Service, Manchester University NHS Foundation Trust, Manchester, UK.
Recurrence of mucocutaneous herpes simplex virus (HSV) infections is common in immunosuppressed patients. Thymidine kinase mutations conferring resistance to the antiviral agent aciclovir have been observed in such patients. Recommended second-line therapeutic agents against HSV are associated with significant side effects contributing to disease burden.
View Article and Find Full Text PDFHerpes Simplex Virus Shedding Rate: Surrogate Outcome for Genital Herpes Recurrence Frequency and Lesion Rates, and Phase 2 Clinical Trials End Point for Evaluating Efficacy of Antivirals.
J Infect Dis
October 2018
Department of Medicine, University of Washington, Seattle, Washington.
Background: We tested whether genital herpes simplex virus (HSV) shedding is an appropriate surrogate outcome for the clinical outcome of genital herpes lesions in studies of HSV-2 antiviral interventions.
Methods: We analyzed prospective data from natural history studies and clinical trials of antiviral agents for HSV-2 in which HSV-2-seropositive participants provided self-collected anogenital swab specimens daily over ≥25 days for HSV DNA quantitation by polymerase chain reaction (PCR). Genital recurrences were self-reported.
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