Abstract |
Feline infectious peritonitis (FIP) is a feline coronavirus (FCoV)-induced fatal disease in wild and domestic cats. FCoV exists in two serotypes. Type I FCoV is the dominant serotype worldwide. Therefore, it is necessary to develop antiviral drugs against type I FCoV infection. We previously reported that type I FCoV is closely associated with cholesterol throughout the viral life cycle. In this study, we investigated whether U18666A, the cholesterol synthesis and transport inhibitor, shows antiviral effects against type I FCoV. U18666A induced cholesterol accumulation in cells and inhibited type I FCoV replication. Surprisingly, the antiviral activity of U18666A was suppressed by the histone deacetylase inhibitor (HDACi), Vorinostat. HDACi has been reported to revert U18666A-induced dysfunction of Niemann-Pick C1 (NPC1). In conclusion, these findings demonstrate that NPC1 plays an important role in type I FCoV infection. U18666A or other cholesterol transport inhibitor may be considered as the antiviral drug for the treatment of cats with FIP.
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Authors | Tomomi Takano, Misaki Endoh, Hiroaki Fukatsu, Haruko Sakurada, Tomoyoshi Doki, Tsutomu Hohdatsu |
Journal | Antiviral research
(Antiviral Res)
Vol. 145
Pg. 96-102
(Sep 2017)
ISSN: 1872-9096 [Electronic] Netherlands |
PMID | 28780424
(Publication Type: Journal Article)
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Copyright | Copyright © 2017 Elsevier B.V. All rights reserved. |
Chemical References |
- Androstenes
- Anticholesteremic Agents
- Histone Deacetylase Inhibitors
- Hydroxamic Acids
- 3-beta-(2-(diethylamino)ethoxy)androst-5-en-17-one
- Vorinostat
- Cholesterol
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Topics |
- Androstenes
(pharmacology)
- Animals
- Anticholesteremic Agents
(pharmacology)
- Cats
- Cholesterol
(metabolism)
- Coronavirus Infections
(drug therapy, virology)
- Coronavirus, Feline
(drug effects)
- Drug Discovery
- Feline Infectious Peritonitis
(drug therapy, virology)
- Histone Deacetylase Inhibitors
(pharmacology)
- Hydroxamic Acids
(pharmacology)
- Virus Replication
(drug effects)
- Vorinostat
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