April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Efficacy of ASP2151, a Novel Herpes Virus Helicase-Primase Inhibitor, in the Mouse Model of Herpes Simplex Keratitis
Author Affiliations & Notes
  • Shin-ichi Sasaki
    Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Yonago, Japan
  • Tomoko Haruki
    Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Yonago, Japan
  • Yukimi Yamamoto
    Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Yonago, Japan
  • Michiko Kandori
    Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Yonago, Japan
  • Keiko Yakura
    Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Yonago, Japan
  • Dai Miyazaki
    Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Yonago, Japan
  • Hiroshi Suzuki
    Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Japan
  • Yoshitsugu Inoue
    Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Yonago, Japan
  • Footnotes
    Commercial Relationships  Shin-ichi Sasaki, None; Tomoko Haruki, None; Yukimi Yamamoto, None; Michiko Kandori, None; Keiko Yakura, None; Dai Miyazaki, None; Hiroshi Suzuki, Astellas Pharma Inc. (E); Yoshitsugu Inoue, Astellas Pharma Inc. (F)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 2062. doi:
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      Shin-ichi Sasaki, Tomoko Haruki, Yukimi Yamamoto, Michiko Kandori, Keiko Yakura, Dai Miyazaki, Hiroshi Suzuki, Yoshitsugu Inoue; Efficacy of ASP2151, a Novel Herpes Virus Helicase-Primase Inhibitor, in the Mouse Model of Herpes Simplex Keratitis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2062.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : We have reported ASP2151, a novel antiviral agent with helicase-primase inhibitor activity, has more potency against herpes simplex virus (HSV) than acyclovir in vitro. In this study we investigated the efficacy of ASP2151 in vivo, using the mouse model of primary herpes simplex keratitis.

Methods: : BALB/c mice were infected with HSV-1 (CHR-3 strain, 2.3×105 PFU/eye) on their right eye. At forty-eight hours post-infection, oral administration of ASP2151 (100mg/kg), valacyclovir (100mg/kg), or vehicle for 5 days was initiated to the mice which had been confirmed the appearance of epithelial dendritic keratitis. The effect of ASP2151, acyclovir or vehicle as an ointment administration was also investigated. Corneal epithelial lesions were graded as 0-4 scores (depending on the lesion severity) every day. Also tear film was collected to measure the amount of HSV-DNA by real-time PCR. After observation period, mice were sacrificed, and HSV-DNA measurement or HSV titration by plaque assay was performed using excised eyes and trigeminal ganglia.

Results: : Orally administered ASP2151 significantly suppressed clinical scores of corneal epithelial lesions (P<0.01) compared with vehicle group, and the amount of HSV-DNA in tear in ASP2151 group was significantly lower than that in valacyclovir and vehicle groups (P<0.01). Also ASP2151 ointment significantly suppressed clinical scores of corneal epithelial lesions compared with vehicle group (P<0.01), however at the later stage, corneal opacities due to side effect of drug or vehicle were observed. Compared to acyclovir, the amount of HSV-DNA in tear was significantly decreased in ASP2151 group (P<0.01). HSV was detected with a highest titer of 7.3×104 PFU/ml in the eye of vehicle-treated mice, but not in drug-treated mice. The amount of HSV-DNA in contralateral trigeminal ganglia was significantly reduced in drug-treated mice compared with vehicle-treated mice (P<0.01).

Conclusions: : The efficacy of ASP2151 for herpes simplex keratitis is superior to valacyclovir/acyclovir in both systemic and local use. Considering the side effect associated with the local use in the experiment, the further study is warranted to improve the formulation of ASP2151 ointment for clinical use.

Keywords: antiviral drugs • herpes simplex virus 
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