Susceptibility of Herpes Simplex Virus Isolated from Genital Herpes Lesions to ASP2151, a Novel Helicase-Primase Inhibitor
Open Access
- 1 July 2012
- journal article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 56 (7), 3587-3591
- https://doi.org/10.1128/aac.00133-12
Abstract
ASP2151 (amenamevir) is a helicase-primase inhibitor against herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus. To evaluate the anti-HSV activity of ASP2151, susceptibility testing was performed on viruses isolated from patients participating in a placebo- and valacyclovir-controlled proof-of-concept phase II study for recurrent genital herpes. A total of 156 HSV strains were isolated prior to the dosing of patients, and no preexisting variants with less susceptibility to ASP2151 or acyclovir (ACV) were detected. ASP2151 inhibited HSV-1 and HSV-2 replication with mean 50% effective concentrations (EC 50 s) of 0.043 and 0.069 μM, whereas ACV exhibited mean EC 50 s of 2.1 and 3.2 μM, respectively. Notably, the susceptibilities of HSV isolates to ASP2151 and ACV were not altered after dosing with the antiviral agents. Taken together, these results demonstrate that ASP2151 inhibits the replication of HSV clinical isolates more potently than ACV, and HSV resistant to this novel helicase-primase inhibitor as well as ACV may not easily emerge in short-term treatment for recurrent genital herpes patients.Keywords
This publication has 25 references indexed in Scilit:
- ASP2151 for the Treatment of Genital Herpes: A Randomized, Double-Blind, Placebo- and Valacyclovir-Controlled, Dose-Finding StudyThe Journal of Infectious Diseases, 2012
- Effect of ASP2151, a Herpesvirus Helicase-Primase Inhibitor, in a Guinea Pig Model of Genital HerpesMolecules, 2011
- Detection of HSV-1 variants highly resistant to the helicase–primase inhibitor BAY 57-1293 at high frequency in 2 of 10 recent clinical isolates of HSV-1Journal of Antimicrobial Chemotherapy, 2007
- Herpes Simplex Virus Resistance to Acyclovir and Penciclovir after Two Decades of Antiviral TherapyClinical Microbiology Reviews, 2003
- Herpes simplex virus antiviral drug resistance — current trends and future prospectsJournal of Clinical Virology, 2001
- Frequency of Acyclovir-Resistant Herpes Simplex Virus in Clinical Specimens and Laboratory IsolatesJournal of Clinical Microbiology, 2001
- Herpes Simplex VirusesClinical Infectious Diseases, 1998
- Virologic Characteristics of Subclinical and Symptomatic Genital Herpes InfectionsNew England Journal of Medicine, 1995
- Laboratory studies of herpes simplex virus strains resistant to acyclovirReviews in Medical Virology, 1991
- Recurrences after Oral and Genital Herpes Simplex Virus InfectionNew England Journal of Medicine, 1987