The broader impact of this Small Business Innovation Research (SBIR) Phase I project will result from development of a safe and sustainable anti-viral treatment for COVID-19. Vaccine and drug development efforts are underway, but the efficacy of these treatments and their safety particularly for high-risk populations remain a concern. The proposed project is an anti-viral inhaler that delivers a natural immune defense salivary protein that blocks the activity of a molecule essential for viral replication in the lung. The candidate therapeutic will potentially be a safer treatment option for people with compromised health. The sustainability of this treatment relies on three factors. First, the therapeutic targets a viral genome replication process. Thus, this targeted technology will not be compromised by virus mutations and will maintain its efficacy against current and future coronavirus outbreaks. Second, it does not require clinical administration and is thus more easily accessible by patients. Third, the treatment has potential as an broad anti-viral therapy. The proposed project will validate a novel anti-viral treatment against SARS-CoV-2. First, the anti-viral action will be validated in a cell-based model that mimics human lung infected with coronavirus, alveolar epithelial cells cultured in an air-liquid interface and infected with SARS-CoV-2. Next, an in vivo model will be used to confirm that the therapy can reach the virus target site in the lung, undergo uptake by the alveolar epithelial cells and avoid the barriers of pulmonary delivery (e.g. mucus, pulmonary enzymes or macrophages). Finally, this project will confirm that the therapy does not elicit a pro-inflammatory response and toxicity in lung cells, so it can be safely given to people with compromised health without exacerbating their immune response. The treatment will be delivered by inhalation and ultimately become a therapeutic and prophylactic anti-viral inhaler. 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.
