Use of Small Molecules to Abrogate the Intracellular Effects of Ebolavirus Protein 24

Michael Pribula, John Carroll University

Abstract

There have been 28,639 cases and 11,316 deaths as a result of the 2014 Ebolavirus outbreak1. Ebolavirus inhibits the immune system, which contributes to its severity. Specifically, the Ebolavirus Protein 24 (eVP24) interferes with the JAK-STAT signaling pathway, which governs production of antiviral proteins. There are currently no FDA approved treatments for Ebolavirus. Our lab identified several molecules that function to enhance the JAK-STAT pathway. It is my hypothesis that these compounds could counter the effects of eVP24. To date, I have expressed eVP24 in mammalian cells. In the future, I will use the subcellular localization of phosphorylated-STAT1 to demonstrate the ability of eVP24 to disrupt nuclear shuttling. Further studies will then address the ability of our compounds to overcome this eVP24-mediated disturbance in trafficking. It is my goal to determine if modulation of the JAK-STAT pathway serves as a viable therapeutic intervention for this deadly disease.