2012年2月
Efficacy of ASP2151, a helicase-primase inhibitor, against thymidine kinase-deficient herpes simplex virus type 2 infection in vitro and in vivo
ANTIVIRAL RESEARCH
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- 巻
- 93
- 号
- 2
- 開始ページ
- 301
- 終了ページ
- 304
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.antiviral.2011.11.015
- 出版者・発行元
- ELSEVIER SCIENCE BV
ASP2151 was developed as a novel inhibitor of herpes simplex virus (HSV) and varicella-zoster virus helicase-primase. The anti-HSV activity of ASP2151 toward a clinical HSV isolate with acyclovir (ACV)-resistant/thymidine kinase (TK)-deficiency was characterized in vitro and in vivo using a plaque reduction assay and the ear pinna infection in mice. The IC50 ranged from 0.018 to 0.024 mu g/ml, indicating the susceptibility of TK-deficient HSV-2 was similar to that of wild-type HSV-2 strains. Anti-HSV activity of ASP2151 in vivo was evaluated in mice infected with wild-type HSV-2 and TK-deficient HSV-2. ASP2151 significantly reduced the copy numbers of wild-type HSV-2 and TK-deficient HSV-2 at the inoculation ear pinna, while valacyclovir significantly reduced the copy number of wild type HSV-2 but not that of TK-deficient HSV-2 in the inoculated ear pinna. Thus, ASP 2151 showed therapeutic efficacy in mice infected with both wild-type and TK-deficient HSV-2. In conclusion, ASP2151 is a promising novel herpes helicase-primase inhibitor that indicates the feasibility of ASP2151 for clinical application for the treatment of HSV infections, including ACV-resistant/TK-deficient HSV infection. (C) 2011 Elsevier B.V. All rights reserved.
- リンク情報
- ID情報
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- DOI : 10.1016/j.antiviral.2011.11.015
- ISSN : 0166-3542
- PubMed ID : 22155691
- Web of Science ID : WOS:000300863500013