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Effect of ASP2151, a Herpesvirus Helicase-Primase Inhibitor, in a Guinea Pig Model of Genital Herpes
Drug Discovery Research, Astellas Pharma Inc., 21, Miyukigaoka, Tsukuba, Ibaraki, Japan
* Author to whom correspondence should be addressed.
Received: 26 July 2011; in revised form: 4 August 2011 / Accepted: 22 August 2011 / Published: 25 August 2011
(This article belongs to the Special Issue Antivirals
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
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MDPI and ACS Style
Katsumata, K.; Chono, K.; Sudo, K.; Shimizu, Y.; Kontani, T.; Suzuki, H. Effect of ASP2151, a Herpesvirus Helicase-Primase Inhibitor, in a Guinea Pig Model of Genital Herpes. Molecules 2011, 16, 7210-7223.
Katsumata K, Chono K, Sudo K, Shimizu Y, Kontani T, Suzuki H. Effect of ASP2151, a Herpesvirus Helicase-Primase Inhibitor, in a Guinea Pig Model of Genital Herpes. Molecules. 2011; 16(9):7210-7223.
Katsumata, Kiyomitsu; Chono, Koji; Sudo, Kenji; Shimizu, Yasuaki; Kontani, Toru; Suzuki, Hiroshi. 2011. "Effect of ASP2151, a Herpesvirus Helicase-Primase Inhibitor, in a Guinea Pig Model of Genital Herpes." Molecules 16, no. 9: 7210-7223.