SUMMARY STATEMENT The SARS-CoV-2 virus depends upon two proteases for replication, 3CLpro and PLpro. If one or both of these proteases can be blocked, COVID-19 infection can be effectively treated. Montana Molecular makes and sells live cell, fluorescent biosensor assays for disease research and drug discovery. In response to the COVID-19 pandemic, Montana Molecular applied its expertise and background in live cell assay development to build fluorescent biosensors for the SARS-CoV-2 main protease, 3CLpro. The prototype sensor described in this proposal demonstrates feasibility. Direct to Phase II support is requested here to speed the development of even brighter, more sensitive assays for the 3CLpro and PLpro proteases. These assays can be used in high throughput screening for compounds that inhibit the protease, and engage with their target in living, human cells. 406-539-7399 366 Gallatin Park Drive Suite A Bozeman, MT 59715

Project Narrative COVID-19 continues to impact nearly every aspect of human health and well-being. Two SARS-CoV-2 proteases are crucial to viral replication and are promising targets for therapeutic drugs to effectively treat COVID-19. Montana Molecular seeks support to create, optimize and test new live cell assays that will be essential tools in the hunt for coronavirus protease inhibitors.These live cell assays will speed the discovery of safer and more effective COVID-19 therapeutics by reporting biological activity of potential inhibitors in living cells. Direct to Phase II support is requested to respond to this challenge with an aggressive time line that is consistent with the urgency of the worldwide effort to combat COVID19. 366 Gallatin Park Drive Suite A Bozeman, MT 59715