SBIR Phase I: Stress Pathway Inhibition Prevents COVID-19 Infection (COVID-19)

The broader impact of this Small Business Innovation Research (SBIR) Phase I project is the pursuit of developing a first-in-class, non-toxic, inexpensive, and effective treatment for COVID-19 for vulnerable patients including the elderly and those at additional risk from cancer, high blood pressure, diabetes and obesity. These conditions produce high levels of stress on diseased cells compared to normal cells. This project leverages insights that COVID-19 uses the same pathway to enhance viral infection as cancer cells use for survival; this process causes immune system weakening which allows tumor cells and viruses to multiply. The proposed project will create innovative anti-viral therapies by exploring how this survival pathway increases COVID-19 infectivity, weakens the immune system and induces tumor cell resistance. Its use can be expanded to other new targets and therapies. This SBIR Phase I project leverages insights regarding similarities between tumors and viral infections. This project will advance translation of a novel inhibitor to a survival factor that continually keeps these wounds from healing by increasing tumor survival and enhancing viral infections. This novel inhibitor can potently block the binding of COVID-19 spike protein to this survival factor, which has been shown to be highly expressed on stressed lung cells as a result of cancer and other inflammatory diseases. The goals of this project are to 1) show that the proposed COVID-19 inhibitor can block COVID-19 infection of stressed lung cells; 2) reduce cytokine expression to lessen the cytokine storm associated with COVID-19 infection; 3) prevent immune weakening and 4) inhibit coagulopathy to lessen the “blood clot storm”. The project will use standard in vitro viral infectivity assays and in vivo immune competent tumor-bearing mice models infected with a lethal strain of COVID-19. Together, these studies will demonstrate that the proposed lead survival factor inhibitor can significantly reduce the attachment, entry and replication of COVID-19 virus as well as reduce the immune suppressive nature of infected lung alveolar epithelial cells in vitro and in vivo. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.