Effect of ASP2151, a Herpesvirus Helicase-Primase Inhibitor, in a Guinea Pig Model of Genital HerpesReportar como inadecuado




Effect of ASP2151, a Herpesvirus Helicase-Primase Inhibitor, in a Guinea Pig Model of Genital Herpes - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Drug Discovery Research, Astellas Pharma Inc., 21, Miyukigaoka, Tsukuba, Ibaraki, Japan





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Abstract ASP2151 is a herpesvirus helicase-primase inhibitor with antiviral activity against varicella zoster virus and herpes simplex virus types 1 HSV-1 and 2 HSV-2. Here, we examined the potency and efficacy of ASP2151 against HSV in vitro and in vivo. We found that ASP2151 was more potent in inhibiting the replication of HSV-1 and HSV-2 in Vero cells in the plaque reduction assay and had greater anti-HSV activity in a guinea pig model of genital herpes than did acyclovir and valacyclovir VACV, respectively. Oral ASP2151 given from the day of infection reduced peak and overall disease scores in a dose-dependent manner, resulting in complete prevention of symptoms at the dose of 30 mg-kg. The 50% effective dose ED50 values for ASP2151 and VACV were 0.37 and 68 mg-kg, respectively, indicating that ASP2151 was 184-fold more potent than VACV. When ASP2151 was administered after the onset of symptoms, the disease course of genital herpes was suppressed more effectively than by VACV, with a significant reduction in disease score observed one day after starting ASP2151 at 30 mg-kg, whereas the therapeutic effect of VACV was only evident three days after treatment at the highest dose tested 300 mg-kg. This indicated that ASP2151 possesses a faster onset of action and wider therapeutic time window than VACV. Further, virus shedding from the genital mucosa was significantly reduced with ASP2151 at 10 and 30 mg-kg but not with VACV, even at 300 mg-kg. Taken together, our present findings demonstrated the superior potency and efficacy of ASP2151 against HSV.

Keywords: ASP2151; amenamevir; antiviral; HSV; guinea pig; genital herpes ASP2151; amenamevir; antiviral; HSV; guinea pig; genital herpes





Autor: Kiyomitsu Katsumata, Koji Chono, Kenji Sudo, Yasuaki Shimizu, Toru Kontani and Hiroshi Suzuki *

Fuente: http://mdpi.com/



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