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

RAPID：使用富含从头设计的中和肽的工程水纳米结构来阻止 SARS-CoV-2 在表面和空气中的传播

• 批准号: 2031785
• 负责人: Philip Demokritou
• 金额: $ 20万
• 依托单位: Harvard University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2031785&HistoricalAwards=false
• 关键词: RAPID; Arresting; spread; SARS; CoV

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.

最近的新冠肺炎疫情凸显了传染病快速传播的问题。新冠肺炎病毒通过受污染的表面和空气传播给新的宿主。众所周知，这种病毒可以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、频繁洗手和社交距离，都是不够的，并造成其他损害，而大量无症状病例和有效口罩的短缺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，都有严重的缺点和健康风险，不能在有人在场的室内实施。该项目寻求利用最近开发的(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灭活病毒。如果这项技术被证明是成功的，它可以被放大，系统可以被建造并用于各种应用。这项创新技术特别适用于封闭的室内环境，随着人们走出社交孤立状态，重返工作岗位，它可能有助于抗击新冠肺炎大流行。作为该项目的一部分，将招募研究生和博士后，并对他们进行跨学科研究培训。通过该项目获得的知识将导致更好地控制和预防新冠肺炎威胁。在这个快速的项目中，将使用新的计算方法从头设计富含二硫键的中和多肽，并使它们具有功能，以结合新冠肺炎的尖峰蛋白，并阻止它与其内源受体血管紧张素转换酶2相互作用。然后，这些多肽将与其他抗菌剂一起被结合到纳米载体平台中，使用电喷雾和电离相结合的方法合成工程水纳米结构。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。这些材料在空气和表面上相互作用和灭活病毒的能力将使用微生物分析进行评估。将合成生物学与纳米技术交织在一起的跨学科方法将为解决环境媒体上的新冠肺炎问题提供一个坚实的工具。此外，该项目还将继续和加强有关环境纳米技术和纳米生物相互作用新方面的教育活动。结果将通过包括出版物、会议和其他外展活动在内的多方面交流活动向相关利益攸关方传播。总而言之，拟议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、无化学物质和环境友好的方法被证明在抗击COVID-19的战斗中有效，那么社会、技术、科学、公共健康和经济影响将是显著的。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。