RAPID: Arresting the spread of SARS-CoV-2 on surfaces and in the air using engineered water nanostructures enriched with de novo designed neutralizing peptides

最近的COVID-19大流行凸显了传染病快速传播的问题。COVID-19病毒通过被污染的表面以及通过空气传播给新的宿主。已知这种病毒可以在空气中存活数小时，在物体表面存活数天。目前所有阻止传播的方法，如戴口罩、经常洗手和保持社交距离，都是不够的，并会造成其他损害，大量无症状病例和缺乏有效口罩正在推动感染人数上升。目前一般预防空气传播传染病的方法，如空气过滤、使用化学气体（如过氧化氢）和使用紫外线辐射，都有重大缺陷和健康风险，而且不能在有人在场的室内实施。本项目旨在利用研究人员最近开发的基于纳米技术的载体平台，利用工程水纳米结构灭活病毒。如果这项技术被证明是成功的，它可以扩大规模，系统可以建立并用于各种应用。这项创新技术特别适用于封闭的室内环境，可以帮助人们摆脱社会隔离状态并重返工作岗位，从而抗击COVID-19大流行。作为该项目的一部分，将招收研究生和博士后，并对其进行跨学科研究培训。通过该项目获得的知识将有助于更好地控制和预防COVID-19威胁。在这个RAPID项目中，将使用新的计算方法来重新设计富含二硫的中和肽，并使其功能化，以结合COVID-19刺突蛋白，并阻断其与内源性受体血管紧张素转换酶2的相互作用。然后，这些肽和其他抗菌剂将被整合到纳米载体平台中，该平台使用电喷雾和电离结合合成的工程水纳米结构。这些水基纳米结构的物理化学性质的全面表征将使用最先进的分析方法进行。这些材料在空气和表面上相互作用和灭活病毒的能力将通过微生物分析进行评估。将合成生物学与纳米技术相结合的跨学科方法将为在环境媒体上应对COVID-19提供坚实的工具。此外，该项目将导致环境纳米技术和纳米生物相互作用新兴方面的教育活动的继续和加强。研究结果将通过包括出版物、会议和其他外联活动在内的多方面沟通活动传播给相关利益攸关方。总之，提出的基于纳米技术的方法有可能改变我们目前控制空气传播传染病的方式。如果这种新颖、可持续、低能耗、无化学品和环境友好的方法在抗击COVID-19的斗争中被证明是有效的，那么社会、技术、科学、公共卫生和经济影响将是巨大的。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 recent COVID-19 pandemic has spotlighted the problem of rapid transmission of infectious diseases. The COVID-19 virus is transmitted to new hosts through contaminated surfaces as well as through the air. The virus is known to survive in air for hours and on surfaces for days. All current approaches for stopping the transmission, such as masks, frequent hand washing, and social distancing, are insufficient and cause other detriments, and the high numbers of asymptomatic cases and shortage of efficient facemasks are driving the number of infections higher. Current methods for general prevention of transmission of airborne infectious diseases, such as air filtration, use of chemical gases (such as hydrogen peroxide) and the use of ultraviolet radiation, have significant shortcomings and health risks, and they cannot be implemented indoors with people present. This project seeks to utilize the recently developed (by the investigators) nanotechnology-based carrier platform using Engineered Water Nanostructures to inactivate viruses. If this technology is proved successful it can be scaled up and systems can be built and used in various applications. This innovative technology is particularly applicable to closed indoor environments and could help in battling the COVID-19 pandemic as people emerge from their social isolation states and return to work. As a part of the project, graduate and postdoctoral students will be recruited and trained in interdisciplinary research. The knowledge gained through the project will lead to better control and prevention of the COVID-19 threat. In this RAPID project, novel computational methods will be used to design neutralizing disulfide-rich peptides de novo and functionalize them to bind the spike protein of COVID-19 and block it from interacting with angiotensin-converting enzyme 2, its endogenous receptor. Then, such peptides, along with other antimicrobials, will be incorporated in a nanocarrier platform using engineered water nanostructures synthesized using combination of electrospray and ionization. A thorough characterization of the physicochemical properties of these water-based nanostructures will be carried out using state of the art analytical methods. The capability of these materials to interact and inactivate the virus on both the air and on surfaces will be assessed using microbiological assays. The interdisciplinary approach of interweaving synthetic biology with nanotechnology would provide a solid tool for tackling COVID-19 on environmental media. Furthermore, the project will lead to the continuation and enhancement of educational activities on emerging aspects of environmental nanotechnology and nano-bio interactions. Results will be disseminated to relevant stakeholders through multifaceted communication activities including publications, conferences, and other out-reach activities. In summary, the proposed nanotechnology-based method has the potential to transform the way we currently control airborne infectious diseases. The social, technological, scientific, public health and economic impact will be significant if such a novel, sustainable, low energy, chemical-free and environmentally friendly method is proven to be effective in the battle against COVID-19.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.