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 now demonstrate in vitro that pyronaridine tetraphosphate is an inhibitor of Lysotracker accumulation in lysosomes (IC₅₀ = 0.56 μM). 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.

中文翻译：

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重新使用Pyramax®来治疗埃博拉病毒病：溶同型吡咯烷和非溶同型青蒿琥酯的可加性

我们最近确定了三种分子（托罗酮，奎纳克林和四磷酸吡喃二胺），它们在小鼠适应埃博拉病毒（EBOV）疾病模型的感染小鼠模型中均显示出功效，并对埃博拉假病毒（VSV-EBOV ）具有相似的体外抑制作用-GP），表明它们会干扰病毒的进入。使用机器学习模型来预测溶溶质的发生，评估这些化合物通过溶溶机理体外抑制的能力。现在，我们在体外证明四磷酸吡喃二甲醚是溶酶体中溶血球蛋白积累的抑制剂（IC ₅₀= 0.56μM）。此外，我们评估了吡咯烷与青蒿琥酯（Pyramax®）的协同作用，两者联合用于治疗疟疾。未发现青蒿琥酯在体外具有溶溶同性活性，并且对EBOV抑制的联合作用已证明是加和的。Pyramax®可能是将组合产品用于另一种疾病的独特例子。