A. Sally Davis
Department of Diagnostic Medicine/Pathobiology
College of Veterinary Medicine, Kansas State University
Characterization of protease TMPRSS2 and its interaction with influenza A (2016-2017)
There is significant need for new antivirals for multiple human and agricultural animal respiratory diseases. We propose to characterize a protease recently discovered to have a role proven in Influenza infections and establish methods to aid in the discovery of antivirals based on blocking its activity and therefore influenza infection.
We seek to understand the role of type II transmembrane serine 1, protease 2 (TMPRSS2) in the proteolytic activation of influenza hemagglutinin protein using both human and porcine TMPRSS2. In vitro and mouse TMPRSS2 knock-out studies clearly show the potential of this host cell protease as an antiviral target for influenza and other respiratory viruses. However, to date, drug discovery efforts as regards inhibition of TMPRSS2 have been disappointing due to the absence of detailed structural and functional information regarding this protease. With the guidance of the Protein Production Group and the Protein Structure Laboratory of the University of Kansas Center of Biomedical Research Excellence in Protein Structure and Function we propose to express active porcine and human TPRSS2 for structural and functional analyses and establish an in vitro assay to study the substrate specificity and inhibitors of TMPRSS2 using a high throughput assay system.