Repurposing Pyramax for the Treatment of Ebola Virus Disease: Additivity of the Lysosomotropic Pyronaridine and Non-Lysosomotropic Artesunate [article]

Thomas R Lane, Julie Dyall, Luke Mercer, Caleb Goodin, Daniel H Foil, Huanying Zhou, Elena Postnikova, Janie Y Liang, Michael Holbrook, Peter Madrid, Sean Ekins
2020 bioRxiv   pre-print
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 inhibit via a lysosomotropic mechanism in vitro. We
more » ... ow demonstrate in vitro that pyronaridine tetraphosphate is an inhibitor of Lysotracker accumulation in lysosomes (IC50 = 0.56 uM). Further, we evaluated 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.
doi:10.1101/2020.04.25.061333 fatcat:fkibhc6d65bdrhevrfursa5cd4