Project Summary/Abstract SARS-CoV-2 infection is associated with high mortality and morbidity worldwide. A common sequela is anosmia, the loss of the sense of smell, which can impact the quality of life severely. This is due to the robust replication of SARS-CoV-2 in the nasal neuroepithelial cells, leading to acute or chronic olfactory dysfunction (anosmia). A significant number of patients in the US (up to 1.6 million) are believed to have lost their sense of smell chronically, and the number is increasing every day. Therefore, a significant gap in treatment/preventive strategies that needs to be filled is to inhibit SARS-CoV-2 replication in the nasal epithelia, and novel approaches and agents are in urgent need to better protect patients from this sensory loss. We hypothesize that EGCG-palmitate (EC16), a compound with broad spectrum of antiviral activities, has potential to become a new drug agent against SARS-CoV-2 replication in nasal epithelial cells, thereby minimizing post COVID- 19 anosmia. EGCG is a natural antioxidant extracted from green tea leaves. Previously published research data, including ours, indicate that although EGCG is a potent inhibitor of diverse groups of viruses, it is not suitable for nasal formulations due to rapid auto-oxidation. We found that EGCG- palmitate, or EC16 (palmitoylated EGCG) is more effective and stable than EGCG, therefore suitable for nasal formulations. The current STTR Phase I proposal is designed to test the proof-of-concept that nasal formulations containing EC16 are able to inhibit coronavirus replication in human nasal epithelial cells. Camellix, LLC, a biotech company associated with Augusta University, is now using this patented technology to develop virucidal and sporicidal hand hygiene and disinfectant products, with promising results. In the current proposal, investigators from Camellix Research Laboratory and Augusta University will test the in vitro efficacy and suitability of novel nasal formulations containing EC16 against two types of human coronaviruses. The proposed work will lead to novel prototypes containing EC16 to provide the basis for future development of new medications against post-COVID-19 anosmia.