Repurposing Pyramax®, quinacrine and tilorone as treatments for Ebola virus disease

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. •We describe a machine learning model to predict lysosomotropic activity.•We demonstrate that pyronaridine, quinacrine and tilorone all inhibit lysotracker accumulation as predicted.•Artesunate does not appear to inhibit lysostracker accumulation as predicted.•We demonstrate additivity between pyronaridine and artesunate for their in vitro EBOV activity.•These findings suggest pyronaridine and artesunate may be combined and repurposed against EBOV.