Efficacy of ASP2151, a helicase–primase inhibitor, against thymidine kinase-deficient herpes simplex virus type 2 infection in vitro and in vivo
| Autor: | Koji Chono, Takehiro Himaki, Hiroshi Suzuki, Tomoko Okuda, Kimiyasu Shiraki, Yumi Masui, Masaya Takemoto, Bo Haixia, Tohru Daikoku |
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| Rok vydání: | 2012 |
| Předmět: |
Herpesvirus 2
Human viruses DNA Primase medicine.disease_cause Antiviral Agents Thymidine Kinase Herpesviridae Virus Cell Line Mice Viral Proteins In vivo Virology Alphaherpesvirinae medicine Animals Humans Aciclovir Enzyme Inhibitors Pharmacology Mice Inbred BALB C Oxadiazoles biology DNA Helicases Wild type Herpes Simplex biology.organism_classification Herpes simplex virus Thymidine kinase Female medicine.drug |
| Zdroj: | Antiviral Research. 93:301-304 |
| ISSN: | 0166-3542 |
| Popis: | 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 μg/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. |
| Databáze: | OpenAIRE |
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