EAGER: Bioengineered Nanobarrier to Protect Against SARS-Cov-2 and Other Viral Infections of the Nasopharynx

2019年冠状病毒病（COVID-19）大流行极大地影响了人类的生活方式，已导致全球600多万人死亡。该项目使用局部屏障来增强鼻粘膜的防御能力，这是预防严重急性呼吸综合征冠状病毒2 （SARS CoV-2）感染的一种非常新颖的方法。这个探索性研究（EAGER）项目的早期概念拨款的目的是设计一种鼻腔喷雾剂和新型涂抹器，可以提供一种特殊的涂层，防止病毒和微生物感染。如果进一步发展，这种用户友好的方法有可能有效防止sars - cov -2变体感染人类。此外，这种创新屏障可以减少其他空气传播威胁的风险，例如，可以在流感季节或新出现的大流行病期间迅速使用。所开发的计算机模型也可用于加快制定准确和精确的对策。计划中的研究将为培养工程和生物医学科学专业的学生提供机会，这些学生通过高度跨学科（工程、分子生物学、病毒学和药理学）的研究进行协作，并将加强正在进行的教育和推广活动，重点是吸引代表性不足的少数群体进入这些研究领域。该项目的总体目标是设计一种创新的、可生物降解的纳米屏障（抗病毒涂层），它是安全的，可以广泛部署，以保护公众免受SARS-CoV-2感染。尽管疫苗、口罩规定和保持社交距离等传统方法被用于预防或减少COVID-19的传播，但长期遵守这些方法是一项挑战。因此，迫切需要一种新的感染预防方法。本项目提出了一种用户友好的纳米屏障，旨在通过增强鼻咽通道中发现的粘膜皮肤衬里的防御能力来防止病毒和微生物附着和感染上皮细胞。纳米屏障通过隔离病毒附着、感染和传播所需的必需胆固醇来灭活包膜病毒。该项目有两个主要目标：(1)利用鼻咽腔的3d模拟来优化参数（液滴和递送产品特性），以指导涂抹器的工程设计，使纳米屏障准确沉积到最容易感染COVID-19的区域，便于转化为临床前模型；(2)在经过验证的冠状病毒小鼠模型中评估纳米屏障的功效。最终的纳米屏障将与SARS-CoV-2变体无关，可以快速推出以有效预防感染。本项目中使用的模拟方法将作为开发有针对性的干预措施的平台，优化鼻咽腔的输送。此外，该项目将扩大对SARS-CoV-2变体如何感染及其易感性的认识和理解。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The Coronavirus Disease 2019 (COVID-19) pandemic has dramatically impacted the way humans live and has resulted in more than 6 million deaths worldwide. This project uses a topical barrier to enhance the defense capabilities of the lining found in the nose, which is a highly novel method to prevent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) infections. The aim of this EArly-concept Grant for Exploratory Research (EAGER) project is to engineer a nasal spray and new type of applicator that can deliver a special coating that prevents viral and microbial infection. This user-friendly approach, if further developed, has the potential to be effective in preventing SAR-CoV-2 variants from infecting humans. Moreover, the innovative barrier could reduce the risk of other airborne threats, e.g., could be rapidly employed during the flu seasons or new emerging pandemics. The in silico computational models developed can also be used to expedite the development of accurate and precise countermeasures. The planned studies will provide opportunities to train engineering and biomedical science students who work collaboratively through highly interdisciplinary (engineering, molecular biology, virology and pharmacology) research studies and will enhance ongoing education and outreach activities focused on attracting underrepresented minority groups into these areas of research.The overall goal of this project is to engineer an innovative, biodegradable, nanobarrier (anti viral coating) that is safe and can be widely deployed to protect the public from SARS-CoV-2 infections. Although traditional approaches like vaccines, mask mandates, and social distancing are being used to prevent or reduce the spread of COVID-19, long-term compliance is a challenge. Therefore, a novel approach to infection prevention is urgently needed. This project proposes a user-friendly nanobarrier designed to prevent viral and microbial attachment and infection of epithelial cells by enhancing the defense capabilities of the mucocutaneous lining found in nasopharyngeal passages. The nanobarrier inactivates enveloped viruses by sequestering essential cholesterols required for viral attachment, infection, and transmission. This project has two major objectives: (1) to use 3D-simulation of the nasopharyngeal cavity to optimize the parameters (droplet and delivery product characteristics) to guide the engineering of an applicator for accurate deposition of the nanobarrier to areas most susceptible to COVID-19 infection, facilitating translation into preclinical models, and (2) evaluate the efficacy of the nanobarrier in a validated coronavirus mouse model. The final nanobarrier will be agnostic to SARS-CoV-2 variants and can be quickly rolled-out to effectively prevent infection. The simulation approach used in this project will serve as a platform to develop targeted interventions with optimized delivery into the nasopharyngeal cavity. Additionally, this project will expand knowledge and understanding of how SARS-CoV-2 variants infect as well as their susceptibility.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.