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

含有 EC16 的新型鼻用制剂可最大限度地减少与 COVID-19 相关的嗅觉丧失

• 批准号: 10543912
• 负责人: Stephen Hsu
• 金额: $ 38.5万
• 依托单位: CAMELLIX, LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10543912
• 关键词: 2019-nCoV; ACE2; Acute; Address; Agreement; Air; Anosmia; Antioxidants; Antiviral Agents; Apoptosis; Biotechnology; COVID-19; COVID-19 associated anosmia; COVID-19 impact; COVID-19 pandemic; COVID-19 patient; COVID-19 prevention; COVID-19 test; COVID-19 treatment; Cell surface; Cells; Chronic; Clinical; Collaborations; Consult; Coronavirus; Coronavirus Infections; Data; Development; Disinfectants; Dose; Epigallocatechin Gallate; Epithelial Cells; Exhibits; Formulation; Foundations; Future; Goals; Green tea; Hand; Human; Hygiene; In Vitro; Infection; Inflammation; Laboratory Research; Legal patent; Letters; Methods; Morbidity - disease rate; Nasal Epithelium; Nasal cavity; Neuroepithelial Cells; Norovirus; Nose; Olfactory Epithelium; Olfactory dysfunction; Organism; Palmitates; Patients; Pharmaceutical Preparations; Phase; Plants; Prevention strategy; Preventive treatment; Property; Publishing; Quality of life; Reaction Time; Research; Research Personnel; Respiratory Tract Infections; SARS-CoV-2 infection; SARS-CoV-2 inhibitor; Sensory; Simplexvirus; Small Business Technology Transfer Research; Smell Perception; Symptoms; System; TMPRSS2 gene; Tea; Technology; Testing; Therapeutic; Time; United States; United States National Institutes of Health; Universities; Vaccines; Variant; Vero Cells; Viral; Viral reservoir; Virus; Virus Diseases; Virus Replication; Work; autooxidation; base; betacoronavirus; combat; cytotoxicity; design; drug development; efficacy study; experience; human coronavirus; in vitro testing; in vivo; in vivo evaluation; influenzavirus; inhibitor; mortality; neutralizing antibody; novel; novel strategies; novel therapeutics; pathogen; polyphenol; post-COVID-19; pre-clinical; prophylactic; prototype; remdesivir; safety study; success; transmission process; virucide

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.

项目概要/摘要 SARS-CoV-2 感染与全世界的高死亡率和发病率相关。常见的后遗症 嗅觉丧失，即嗅觉丧失，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大量复制，导致急性或慢性嗅觉障碍 功能障碍（嗅觉丧失）。据信美国有大量患者（多达 160 万） 长期失去嗅觉的人，而且数量每天都在增加。因此，一个 治疗/预防策略中需要填补的重大空白是抑制 SARS-CoV-2 鼻上皮细胞中的复制，迫切需要新的方法和药物来更好地保护 患者免受这种感觉丧失。我们假设 EGCG-棕榈酸酯 (EC16) 是一种化合物 具有广谱抗病毒活性，有潜力成为新药 对抗 SARS-CoV-2 在鼻上皮细胞中的复制，从而最大限度地减少新冠病毒感染后的感染 19 嗅觉丧失。 EGCG是从绿茶叶中提取的天然抗氧化剂。先前发表 研究数据（包括我们的数据）表明，尽管 EGCG 是多种不同组别的有效抑制剂， 病毒，由于快速自动氧化，不适合鼻用制剂。我们发现 EGCG- 棕榈酸酯或 EC16（棕榈酰化 EGCG）比 EGCG 更有效、更稳定，因此适合 用于鼻腔制剂。目前的 STTR 第一阶段提案旨在测试概念验证： 含有EC16的鼻用制剂能够抑制冠状病毒在人鼻上皮中的复制 细胞。 Camellix, LLC 是一家与奥古斯塔大学相关的生物技术公司，目前正在使用这项专利 技术开发杀病毒和杀孢子的手部卫生和消毒产品，前景广阔 结果。在当前的提案中，来自 Camellix 研究实验室和奥古斯塔的研究人员 大学将测试含有 EC16 的新型鼻用制剂的体外功效和适用性 对抗两种类型的人类冠状病毒。拟议的工作将产生包含以下内容的新颖原型： EC16 为未来开发针对 COVID-19 后嗅觉丧失的新药物奠定了基础。