Abstract by Olivia Fisher
Chemistry and Biochemistry
Effects of Protease Inhibitors on Liver Fibrosis
Lung and liver fibrosis are important diseases with few treatments. Transforming Growth Factor-beta (TGF-b) is a cytokine that signals for fibrosis and activates Matrix Metalloproteinase-14 (MMP-14). This stimulates the overproduction of collagen, an important component of fibrosis. TGF-b and MMP-14 are both synthesized as inactive precursors until a protease called Furin cuts these precursors into their active forms. The Watt lab has identified the HIV protease drug Nelfinavir as a Furin inhibitor and showed that Nelfinavir could block the activation of another proprotein called prohepcidin. We propose that Nelfinavir and other HIV protease inhibitors will block the activation of TGF-b and MMP-14 to slow fibrosis. We have used computer docking, enzyme assays, and tissue culture assays to test different HIV protease inhibitors to find the most effective Furin inhibitor. From our research, we determined that Lopinavir, Ataznavir, and Fosamprenavir all inhibit Furin, and identified Fosamprenavir as the most promising Furin inhibitor.