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

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.