Efficacy of ASP2151, a helicase-primase inhibitor, against thymidine kinase-deficient herpes simplex virus type 2 infection in vitro and in vivo

被引：19

作者：

Himaki, Takehiro ^{[1
]}

Masui, Yumi ^{[1
]}

Chono, Koji ^{[2
]}

Daikoku, Tohru ^{[1
]}

Takemoto, Masaya ^{[1
]}

Haixia, Bo ^{[1
]}

Okuda, Tomoko ^{[1
]}

Suzuki, Hiroshi ^{[2
]}

Shiraki, Kimiyasu ^{[1
]}

机构：

[1] Toyama Univ, Dept Virol, Toyama 9300194, Japan

[2] Astellas Pharma Inc, Drug Discovery Res, Tsukuba, Ibaraki 3058585, Japan

来源：

ANTIVIRAL RESEARCH | 2012年 / 93卷 / 02期

关键词：

Herpes simplex viruses; Thymidine kinase; ASP2151; Helicase-primase inhibitor; Resistance; Acyclovir; VARICELLA-ZOSTER-VIRUS; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; ACYCLOVIR-RESISTANT; GENITAL HERPES; TRANSPLANT RECIPIENTS; ANTIVIRAL DRUGS; SENSITIVE VIRUS; REPLICATION; MICE; PATHOGENICITY;

D O I：

10.1016/j.antiviral.2011.11.015

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：301 / 304

页数：4

共 31 条

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