SBIR Phase I: Antiviral and Anti-inflammatory Live Biotherapeutics (COVID-19)

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The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is the development of new therapeutics against coronavirus SARS-CoV-2 and associated COVID-19. Few broad-spectrum antivirals exist, and vaccines are effective but strain-specific and require development time for each new strain. This project will engineer probiotics native to the upper respiratory tract of humans to serve as antiviral and antibacterial agents. These probiotics will inhibit viral entry inside human lung cells and stop lung inflammation that causes lethal severe acute respiratory distress in COVID-19 patients. This development will be enabled by modern synthetic biology techniques and an agile research and development paradigm.This Small Business Innovation Research Phase I project will advance the development of new probiotics. These benign, non-virulent microbes will be equipped with defensins, protegrins and compstatins. Defensins are peptides known to inhibit critical steps in viral infection, including the antagonistic binding of angiotensin converting enzyme 2, the human cell receptor thought to facilitate Covid-19 entry inside lung epithelial cells. Protegrins are broad spectrum antimicrobials, with strong activity against bacteria, such as pneumonia-causing Klebsiella spp. and viral particles, including enveloped viruses like SARS-CoV-2. Compstatin is a complement system inhibitor that modulates the overactivation of inflammatory responses, which in the case of a coronavirus infection results in severe acute respiratory syndrome. At the end of this project, a library of live biotherapeutics will be developed that can exhibit antiviral, antibacterial and anti-inflammatory activity when expressing and secreting combinations of peptides.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.