The cholesterol transport inhibitor U18666A inhibits type I feline coronavirus infection

Antiviral Res. 2017 Sep;145:96-102. doi: 10.1016/j.antiviral.2017.07.022. Epub 2017 Aug 3.

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.

Keywords: Cholesterol; Feline coronavirus; Histone deacetylase inhibitor; NPC1; U18666A.

MeSH terms

  • Androstenes / pharmacology*
  • Animals
  • Anticholesteremic Agents / pharmacology*
  • Cats
  • Cholesterol / metabolism
  • Coronavirus Infections / drug therapy
  • Coronavirus Infections / virology
  • Coronavirus, Feline / drug effects*
  • Drug Discovery
  • Feline Infectious Peritonitis / drug therapy
  • Feline Infectious Peritonitis / virology
  • Histone Deacetylase Inhibitors / pharmacology
  • Hydroxamic Acids / pharmacology
  • Virus Replication / drug effects
  • Vorinostat

Substances

  • Androstenes
  • Anticholesteremic Agents
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • 3-beta-(2-(diethylamino)ethoxy)androst-5-en-17-one
  • Vorinostat
  • Cholesterol