The broader impact / commercial potential of this Small Business Technology Transfer (STTR) Phase I project is to develop a new therapeutic for the SARS-CoV-2 virus causing COVID-19. The proposed technology is a novel therapeutic engineered to specifically target the coronavirus and assemble on its surface, disabling the virusâ infectivity. This therapeutic will potentially protect COVID-19 patients with mild to moderate symptoms from worsening and possibly transmitting the virus. The therapy may later benefit asymptomatic or non-infected high-risk groups as well. This Small Business Technology Transfer (STTR) Phase I project will study the nature of supramolecular assembly of self-assembled peptides (SAPs) on the surface of pathogens such as the COVID-19 virus (SARS-CoV-2) and its impact on the impairment and immune recognition of the pathogen. Self-assembled peptides have greater stability than unfunctionalized peptides, yet they are twenty times smaller than antibodies. Therefore, they may combine key benefits of antibodies and small molecules, enabling a new modality designed for rapid and affordable widespread development of urgently needed therapies. Current repurposing efforts are limited by a lack of specificity, while SARS-CoV-2-specific efforts are dominated by antibodies or proteins that are challenging to rapidly manufacture at scale. We will: (1) engineer functionalized anti-COVID-19 SAPs and studying their binding kinetics to the SARS-CoV-2 viral spike protein receptor binding domain (RBD); (2) investigate the in vitro efficacy of anti-COVID-19 SAPs in inhibiting viral infection; and (3) establish the in vitro cytocompatibility and in vivo dose range tolerability of the SAPs. 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