Molecules 2011, 16(9), 7210-7223; doi:10.3390/molecules16097210
Article

Effect of ASP2151, a Herpesvirus Helicase-Primase Inhibitor, in a Guinea Pig Model of Genital Herpes

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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)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.

AMA 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(9):7210-7223.

Chicago/Turabian Style

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.

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