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 (ED(50)) 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.