Effect of ASP2151, a Herpesvirus Helicase-Primase Inhibitor, in a Guinea Pig Model of Genital Herpes
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 inhibiti...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2011-08-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1420-3049/16/9/7210/ |
| _version_ | 1818268358495174656 |
|---|---|
| author | Toru Kontani Yasuaki Shimizu Kenji Sudo Koji Chono Kiyomitsu Katsumata Hiroshi Suzuki |
| author_facet | Toru Kontani Yasuaki Shimizu Kenji Sudo Koji Chono Kiyomitsu Katsumata Hiroshi Suzuki |
| author_sort | Toru Kontani |
| collection | DOAJ |
| description | 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 (ED50) 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. |
| first_indexed | 2024-12-12T20:37:13Z |
| format | Article |
| id | doaj.art-6f6a95645a4d4d7f9182203bc6149f62 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-12T20:37:13Z |
| publishDate | 2011-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-6f6a95645a4d4d7f9182203bc6149f622022-12-22T00:12:52ZengMDPI AGMolecules1420-30492011-08-011697210722310.3390/molecules16097210Effect of ASP2151, a Herpesvirus Helicase-Primase Inhibitor, in a Guinea Pig Model of Genital HerpesToru KontaniYasuaki ShimizuKenji SudoKoji ChonoKiyomitsu KatsumataHiroshi SuzukiASP2151 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 (ED50) 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.http://www.mdpi.com/1420-3049/16/9/7210/ASP2151amenamevirantiviralHSVguinea piggenital herpes |
| spellingShingle | Toru Kontani Yasuaki Shimizu Kenji Sudo Koji Chono Kiyomitsu Katsumata Hiroshi Suzuki Effect of ASP2151, a Herpesvirus Helicase-Primase Inhibitor, in a Guinea Pig Model of Genital Herpes Molecules ASP2151 amenamevir antiviral HSV guinea pig genital herpes |
| title | Effect of ASP2151, a Herpesvirus Helicase-Primase Inhibitor, in a Guinea Pig Model of Genital Herpes |
| title_full | Effect of ASP2151, a Herpesvirus Helicase-Primase Inhibitor, in a Guinea Pig Model of Genital Herpes |
| title_fullStr | Effect of ASP2151, a Herpesvirus Helicase-Primase Inhibitor, in a Guinea Pig Model of Genital Herpes |
| title_full_unstemmed | Effect of ASP2151, a Herpesvirus Helicase-Primase Inhibitor, in a Guinea Pig Model of Genital Herpes |
| title_short | Effect of ASP2151, a Herpesvirus Helicase-Primase Inhibitor, in a Guinea Pig Model of Genital Herpes |
| title_sort | effect of asp2151 a herpesvirus helicase primase inhibitor in a guinea pig model of genital herpes |
| topic | ASP2151 amenamevir antiviral HSV guinea pig genital herpes |
| url | http://www.mdpi.com/1420-3049/16/9/7210/ |
| work_keys_str_mv | AT torukontani effectofasp2151aherpesvirushelicaseprimaseinhibitorinaguineapigmodelofgenitalherpes AT yasuakishimizu effectofasp2151aherpesvirushelicaseprimaseinhibitorinaguineapigmodelofgenitalherpes AT kenjisudo effectofasp2151aherpesvirushelicaseprimaseinhibitorinaguineapigmodelofgenitalherpes AT kojichono effectofasp2151aherpesvirushelicaseprimaseinhibitorinaguineapigmodelofgenitalherpes AT kiyomitsukatsumata effectofasp2151aherpesvirushelicaseprimaseinhibitorinaguineapigmodelofgenitalherpes AT hiroshisuzuki effectofasp2151aherpesvirushelicaseprimaseinhibitorinaguineapigmodelofgenitalherpes |