I received my bachelor’s degree in Chemistry and Biochemistry from the University of Nebraska-Lincoln in May 2013. My undergraduate research focused on ionic liquid supercapacitors in Dr. Redepenning’s lab. Currently, I am entering my fourth year in the Medicinal Chemistry and Molecular Pharmacology graduate program at Purdue University. My research focuses on synthesizing and testing natural product derivatives that target human vacuolar-ATPase as therapies for Ebolavirus infection. In the future, I would like to work further on the development of infectious disease-oriented medicinal chemistry.
Filoviruses (Ebolavirus and related viruses) are highly contagious, lethal pathogens that cause severe hemorrhagic fever in humans and primates. Currently, there are no approved therapeutic measures for the treatment of filovirus infections, which makes their development of paramount importance. A promising therapeutic target is the infection of macrophages and dendritic cells early in the Filovirus lifecycle. Therefore, targeting viral inhibitors to the host lysosomes of macrophages could prevent systemic and deadly filovirus infection. The cellular enzyme vacuolar-ATPase (v-ATPase) has been identified as integral to the entry of filoviruses into host cells. Our hypothesis is that by inhibiting the cellular enzyme vacuolar-ATPase (v-ATPase) in macrophages, we will prevent the infection of these cells by Ebolavirus and reduce the spread of the virus throughout the body. The discovery of the V-ATPase inhibitory properties of the naturally-occurring lignan diphyllin presents a new chemical entity that is distinct from all previously known v-ATPase inhibitors. Diphyllin is a arylnaphthalene lignan, found in plants and has shown promising anti-tumor and anti-osteoclast activity, as well as strong anti-viral activity against Influenza. We have synthesized several lactam and imide analogues of diphyllin that exhibited potency of ~1µM against cellular ebolavirus entry. Further studies will employ polyamines shown to enhance macrophage selectivity, prodrugs and formulation strategies to enhance macrophage uptake and reduce off-target effects of diphyllin.