Novel Nasal Formulations Containing EC16 for Minimizing COVID-19-Associated Anosmia

项目总结/摘要 SARS-CoV-2感染与全球高死亡率和发病率相关。常见的后遗症 是嗅觉缺失症，嗅觉的丧失，这会严重影响生活质量。这是由于 SARS-CoV-2在鼻神经上皮细胞中的稳健复制，导致急性或慢性嗅觉障碍。 功能障碍（嗅觉丧失）。据信，美国有相当多的患者（高达160万） 长期失去嗅觉，而且每天都在增加。因此 治疗/预防策略中需要填补的一个重大空白是抑制SARS-CoV-2 鼻上皮中的复制，迫切需要新的方法和试剂来更好地保护 患者的这种感觉丧失。我们假设，EGCG-棕榈酸酯（EC 16），一种化合物， 具有广谱的抗病毒活性，有望成为一种新的药物制剂 针对SARS-CoV-2在鼻上皮细胞中的复制，从而最大限度地减少COVID-11后 19名嗅觉丧失。表没食子儿茶素没食子酸酯是从绿色茶叶中提取的天然抗氧化剂。此前公布 包括我们在内的研究数据表明，尽管EGCG是多种细胞的有效抑制剂， 病毒，由于快速自动氧化，它不适合鼻用制剂。我们发现EGCG- 棕榈酸酯或EC 16（棕榈酰化的EGCG）比EGCG更有效和稳定，因此适合 用于鼻用制剂。目前的STTR第一阶段提案旨在测试概念验证， 含有EC 16的鼻用制剂能够抑制人鼻上皮细胞中的冠状病毒复制 细胞Camellix，LLC是一家与奥古斯塔大学有联系的生物技术公司，现在正在使用这项专利技术。 开发杀病毒和杀孢子的手卫生和消毒产品的技术， 结果在目前的提案中，来自Camellix研究实验室和Augusta的研究人员 大学将测试含有EC 16的新型鼻用制剂的体外功效和适用性 对抗两种人类冠状病毒。拟议的工作将导致新的原型， EC 16为未来开发针对COVID-19后嗅觉丧失的新药提供基础。

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.