Abstract | OBJECTIVES: To evaluate and describe the anti-herpesvirus effect of ASP2151, amenamevir, a novel non- nucleoside oxadiazolylphenyl-containing herpesvirus helicase- primase complex inhibitor. METHODS: The inhibitory effect of ASP2151 on enzymatic activities associated with a recombinant HSV-1 helicase- primase complex was assessed. To investigate the effect on viral DNA replication, we analysed viral DNA in cells infected with herpesviruses [herpes simplex virus (HSV), varicella-zoster virus (VZV) and human cytomegalovirus]. Sequencing analyses were conducted on an ASP2151-resistant VZV mutant. In vitro and in vivo antiviral activities were evaluated using a plaque reduction assay and an HSV-1-infected zosteriform-spread model in mice. RESULTS: CONCLUSIONS:
ASP2151 is a novel herpes helicase- primase inhibitor that warrants further investigation for the potential treatment of both VZV and HSV infections.
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Authors | Koji Chono, Kiyomitsu Katsumata, Toru Kontani, Masayuki Kobayashi, Kenji Sudo, Tomoyuki Yokota, Kenji Konno, Yasuaki Shimizu, Hiroshi Suzuki |
Journal | The Journal of antimicrobial chemotherapy
(J Antimicrob Chemother)
Vol. 65
Issue 8
Pg. 1733-41
(Aug 2010)
ISSN: 1460-2091 [Electronic] England |
PMID | 20534624
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antiviral Agents
- Enzyme Inhibitors
- Viral Proteins
- DNA Helicases
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Topics |
- Animals
- Antiviral Agents
(pharmacology, therapeutic use)
- Cytomegalovirus
(drug effects)
- DNA Helicases
(antagonists & inhibitors)
- DNA Mutational Analysis
- Disease Models, Animal
- Drug Resistance, Viral
- Enzyme Inhibitors
(pharmacology, therapeutic use)
- Female
- Herpes Zoster
(drug therapy)
- Herpesvirus 1, Human
(drug effects)
- Herpesvirus 2, Human
(drug effects)
- Herpesvirus 3, Human
(drug effects)
- Mice
- Microbial Sensitivity Tests
- Sequence Analysis, DNA
- Viral Plaque Assay
- Viral Proteins
(antagonists & inhibitors)
- Virus Replication
(drug effects)
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