Development of novel Small Molecule Antiviral Endocytosis Inhibition pathway

Fabrico Technology, Professor Kevin Dalby, the Johnson & Johnson Centennial Professor of Chemical Biology & Medicinal Chemistry, and Dr. Tamer Kaoud, Research Assistant Professor of Chemical Biology & Medicinal Chemistry, College of Pharmacy, the University of Texas at Austin (UT), propose to develop and discover a new family of a small molecule(s) that increases the endosomal pH resulting in inhibiting and blocking Bunyavirus viral entry. We plan to use pseudotyped lentiviral particles bearing Hantavirus glycoproteins to screen for triptan blocker active against viral entry as a proof-of-concept. The proposed inhibition pathway is unique, innovative, and novel and has not been shown in the Bunyavirus family. In Phase I, we plan to (1) Identify inhibitors of pseudovirus entry in cells by adapting pseudotyped lentiviral particle infection to a cell-based screening format, (2) Synthesize/generate pseudotyped lentiviral particles bearing Hantavirus glycoproteins, (3) Optimize screening assay, (4) Screen for small molecule inhibitors, (5) Develop Technology Transitioning Plan, and (5) Develop a Phase II program plan. At the end of Phase I, Fabrico, Professor Dalby, and Dr. Kaoud will have a set of triptan derivatives that would increase the endosomal pH resulting in blockage of the Bunyavirus viral entry minimum to no cytotoxicity.