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疫情凸显了传染病快速传播的问题。COVID-19病毒通过受污染的表面和空气传播给新的宿主。已知该病毒在空气中存活数小时，在表面存活数天。目前所有阻止传播的方法，如口罩、勤洗手和保持社交距离，都是不够的，并导致其他疾病，大量无症状病例和缺乏有效的口罩，导致感染人数增加。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，都有明显的缺点和健康风险，而且不能在有人在场的室内实施。该项目旨在利用最近开发的（由研究人员）基于纳米技术的载体平台，使用工程水纳米结构来抑制病毒。如果这项技术被证明是成功的，它可以扩大规模，系统可以建立和用于各种应用。这项创新技术特别适用于封闭的室内环境，并有助于对抗COVID-19大流行，因为人们摆脱了社交隔离状态并重返工作岗位。作为该项目的一部分，将招募研究生和博士后学生进行跨学科研究。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，新的计算方法将用于从头设计富含二硫键的中和肽，并将其功能化，以结合COVID-19的刺突蛋白，并阻止其与其内源性受体血管紧张素转换酶2相互作用。然后，这样的肽，沿着与其他抗菌剂一起，将被掺入到纳米载体平台中，所述纳米载体平台使用利用电喷雾和电离的组合合成的工程化水纳米结构。将使用最先进的分析方法对这些水基纳米结构的物理化学性质进行彻底的表征。将使用微生物测定法评估这些材料与空气和表面上的病毒相互作用和粘附的能力。将合成生物学与纳米技术相结合的跨学科方法将为应对环境媒介上的COVID-19提供坚实的工具。此外，该项目将导致继续和加强关于环境纳米技术和纳米生物相互作用的新方面的教育活动。将通过出版物、会议和其他外联活动等多方面宣传活动，向相关利益攸关方传播成果。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。如果这种新颖的、可持续的、低能耗的、无化学品的和环境友好的方法被证明在对抗COVID-19的斗争中是有效的，那么它将对社会、技术、科学、公共卫生和经济产生重大影响。该奖项反映了NSF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.