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The cholesterol transport inhibitor U18666A inhibits type I feline coronavirus infection.

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.
AuthorsTomomi Takano, Misaki Endoh, Hiroaki Fukatsu, Haruko Sakurada, Tomoyoshi Doki, Tsutomu Hohdatsu
JournalAntiviral research (Antiviral Res) Vol. 145 Pg. 96-102 (Sep 2017) ISSN: 1872-9096 [Electronic] Netherlands
PMID28780424 (Publication Type: Journal Article)
CopyrightCopyright © 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
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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