Inhibition of in vitro Ebola infection by anti-parasitic quinoline derivatives

F1000Res. 2020 Apr 17:9:268. doi: 10.12688/f1000research.22352.1. eCollection 2020.

Abstract

There continues to be no approved drugs for the treatment of Ebola virus disease (EVD). Despite a number of candidate drugs showing limited efficacy in vitro and/or in non-human primate studies, EVD continues to plaque certain areas of Africa without any efficacious treatments yet available. Recently, we have been exploring the potential for anti-malarial drugs to inhibit an in vitro model of Ebola Zaire replication using a transcription-competent virus-like particle (trVLP) assay. We examined the efficacy of chloroquine, amodiaquine and 36 novel anti-parasite quinoline derivatives at inhibiting Ebola virus replication. Drug efficacy was tested by trVLP assay and toxicity by MTT assay. Both chloroquine and amodiaquine were effective for inhibition of Ebola virus replication without significant toxicity. The half-maximal inhibitory concentration (IC 50) of chloroquine and amodiaquine to inhibit Ebola virus replication were IC 50, Chl = 3.95 µM and IC 50, Amo = 1.45 µM, respectively. Additionally, three novel quinoline derivatives were identified as having inhibitory activity and low toxicity for Ebola trVLP replication, with 2NH2Q being the most promising derivative, with an IC 50 of 4.66 µM. Quinoline compounds offer many advantages for disease treatment in tropical climates as they are cheap to produce, easy to synthesize and chemically stable. In this report, we have demonstrated the potential of anti-parasite quinolines for further investigation for use in EVD.

Keywords: Ebola virus; antiparasitic drugs; antiviral activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amodiaquine / pharmacology
  • Antiviral Agents / pharmacology*
  • Chloroquine / pharmacology
  • Ebolavirus / drug effects*
  • Ebolavirus / physiology
  • Quinolines / pharmacology*
  • Virus Replication / drug effects*

Substances

  • Antiviral Agents
  • Quinolines
  • Amodiaquine
  • Chloroquine

Grants and funding

SDSM is a recipient of the Vanier CGS D and Canadian Blood Services GFP graduate awards. DRB is partially funded through support provided by Health Canada, but the views expressed herein to not necessarily represent the view of the federal government of Canada.