Title: Repurposing Pyramax®, quinacrine and tilorone as treatments for Ebola virus disease.
Authors: Lane, Thomas R; Dyall, Julie; Mercer, Luke; Goodin, Caleb; Foil, Daniel H; Zhou, Huanying; Postnikova, Elena; Liang, Janie Y; Holbrook, Michael R; Madrid, Peter B; Ekins, Sean
Published In Antiviral Res, (2020 10)
Abstract: We have recently identified three molecules (tilorone, quinacrine and pyronaridine tetraphosphate) which all demonstrated efficacy in the mouse model of infection with mouse-adapted Ebola virus (EBOV) model of disease and had similar in vitro inhibition of an Ebola pseudovirus (VSV-EBOV-GP), suggesting they interfere with viral entry. Using a machine learning model to predict lysosomotropism these compounds were evaluated for their ability to possess a lysosomotropic mechanism in vitro. We now demonstrate in vitro that pyronaridine tetraphosphate is an inhibitor of Lysotracker accumulation in lysosomes (IC50 = 0.56 μM). Further, we evaluated antiviral synergy between pyronaridine and artesunate (Pyramax®), which are used in combination to treat malaria. Artesunate was not found to have lysosomotropic activity in vitro and the combination effect on EBOV inhibition was shown to be additive. Pyramax® may represent a unique example of the repurposing of a combination product for another disease.
PubMed ID: 32798602
MeSH Terms: Antiviral Agents/pharmacology*; Antiviral Agents/therapeutic use; Artesunate/therapeutic use*; Drug Combinations; Drug Repositioning*; Drug Synergism; Ebolavirus/drug effects*; HeLa Cells; Hemorrhagic Fever, Ebola/drug therapy; Hemorrhagic Fever, Ebola/virology; Humans; Lysosomes/drug effects*; MCF-7 Cells; Machine Learning; Naphthyridines/therapeutic use*; Quinacrine/therapeutic use*; Tilorone/therapeutic use*; Virus Internalization/drug effects