OBJECTIVES/GOALS: Susceptible mucocutaneous membranes of the eye and nasal cavity are easily infected by viruses leading to pink eye or respiratory infections whose direct cost has been estimated as $16 billion annually in the United States. We have developed a novel and effective barrier that will be agnostic to variants enveloped viruses like coronaviruses. METHODS/STUDY POPULATION: We evaluated the efficacy of hydroxypropyl cyclodextrin barrier in preventing respiratory coronavirus infections using 25 humanized angiotensin converting enzyme-2 receptor (hACE-2) mice under a BSL3 laboratory setting. We have shown the barrier is safe and efficacious in preventing coronavirus infections in in vitro respiratory cell lines. We instilled 10 uL aliquot of the barrier into the nostril of the mouse 30 minutes before exposing them to a 10uL titer containing 10,000 plaque forming units of the SARS-CoV-2 delta variant. The control mice received the SARS-CoV-2 infection but not the barrier. The mice were observed for 5 days after which they were sacrificed. We analyzed the lungs and nasal palates for viral load using reverse transcription-polymerase chain reaction. RESULTS/ANTICIPATED RESULTS: We observed our barrier to be effective in preventing SARS-CoV-2 delta variant infection in hACE2 mice models. The lungs and nasal secretions of treated mice were less infectious with lower viral load than the control mice. The lungs of treated mice showed decrease in IFN gene expression and many cytokines and chemokines that regulate virally induced inflammatory responses such as IL-1b, IL-8, CXCL9, CXCL10, and the CCLs. We observed the plasma Angiotensin I and Angiotensin II decreased with barrier treatment, correlating with the viral load observed in the lungs. These peptides may be useful biomarkers for monitoring viral load within the lungs of virally infected individuals. DISCUSSION/SIGNIFICANCE: This supports the barrier’s efficacy to reduce transmission and prevent infections of SARS-CoV-2. This easy to use barrier can augment the mucocutaneous layers of the eye and nasal cavity. Our agnostic barrier will reduce the economic and public health burden of seasonal respiratory and eye viral infections and their related deaths amongst the public.