Repurposing Quinacrine against Ebola Virus Infection In Vivo

Antimicrob Agents Chemother. 2019 Aug 23;63(9):e01142-19. doi: 10.1128/AAC.01142-19. Print 2019 Sep.

Abstract

Quinacrine hydrochloride is a small-molecule, orally bioavailable drug that has been used clinically as an antimalarial and for many other applications. A machine learning model trained on Ebola virus (EBOV) screening data identified quinacrine as a potent (nanomolar) in vitro inhibitor. In the current study, quinacrine 25 mg/kg was shown to protect 70% of mice (statistically significant) from a lethal challenge with mouse-adapted EBOV with once-daily intraperitoneal dosing for 8 days.

Keywords: Ebola virus; Ebola virus disease; antiviral; quinacrine.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antimalarials / pharmacology*
  • Antiviral Agents / pharmacology*
  • Caco-2 Cells
  • Chlorocebus aethiops
  • Disease Models, Animal
  • Drug Repositioning*
  • Ebolavirus / drug effects*
  • Ebolavirus / growth & development
  • HeLa Cells
  • Hemorrhagic Fever, Ebola / drug therapy*
  • Hemorrhagic Fever, Ebola / mortality
  • Hemorrhagic Fever, Ebola / pathology
  • Hemorrhagic Fever, Ebola / virology
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Microbial Sensitivity Tests
  • Quinacrine / pharmacology*
  • Survival Analysis
  • Tilorone / pharmacology
  • Vero Cells
  • Viral Load / drug effects

Substances

  • Antimalarials
  • Antiviral Agents
  • Quinacrine
  • Tilorone