RAPID: Molecular Imprinting of Coronavirus Attachment Factors to Enhance Disinfection by a Selective Photocatalytic “Trap-and-Zap” Approach

导致新冠肺炎的病毒(即SARS-CoV-2)已在通风管道中被发现，这表明它可能通过空调系统在建筑物内传播。尽管患者检测呈阴性，SARS-CoV-2病毒也会在粪便中排放，因此它可能会到达污水处理厂，在那里它可以存活数天，并被雾化或排放到污水中。事实上，有报道称，SARS-CoV-2可能通过浴室管道传播。虽然冠状病毒可以通过一些传统的水处理过程灭活，但迫切需要在现实情况下快速、高效和可靠的更精确的病毒消毒方法。本项目的目标是开发一种新的方法，用于选择性吸附和光催化消毒(即捕集和捕集)SARS-CoV-2和其他致病冠状病毒。这将产生一种无化学物质的技术(从而避免有害的消毒副产品)，具有前所未有的精确度和可靠的灭活冠状病毒的效率。驱动假设是，带有常见冠状病毒附着因子的石墨化碳氮化物的分子印迹将使病毒能够选择性地吸附在反应部位附近，从而产生可靠的高消毒效果。虽然增强废水消毒和医院空气消毒系统的能力和弹性以保护公众健康免受新出现的传染病的影响具有重大的内在价值，但这一项目的好处要广泛得多。该项目将增强对各种冠状病毒(例如，引起新冠肺炎、中东呼吸综合征和SARS的冠状病毒)的表面识别，这将有助于努力将它们集中起来，并提高可用于诊断和监测工作的传感器的精确度分离(例如，通过更好的吸附剂)和检测极限。项目成果将被整合到各种课程中，包括莱斯的教师纳米环境工程(NEET)课程，该课程招收了15名教师，每年接触到3300多名高中生。这门课程最近扩展到亚利桑那州立大学，也正在扩展到埃尔帕索的德克萨斯大学，从而确保在STEM教师中广泛传播这种“陷阱-Zap”方法。该项目建立在最近发表的、纳米技术支持的“Trap-and-Zap”方法(通过分子印迹增强)的基础上，选择性地吸附抗生素耐药基因，并将它们集中在光催化位置附近，以实现有效的降解(doi.org/10.1021/acs.est.9b06926)。这种方法将被改进以针对SARS-CoV-2和其他冠状病毒，方法是将参与病毒附着的分子，如唾液酸、硫酸肝素蛋白多糖和血管紧张素转换酶相关羧肽酶(ACE2)相关肽印迹到石墨化氮化碳光催化剂上。当印迹分子被去除时(例如，通过酸洗)，它会留下一个靶标特定的空腔，以实现选择性吸附和光催化失活，并最大限度地减少背景水成分的干扰。低致病性冠状病毒HCoVNL63(与SARS-CoV2相似，被S刺突蛋白包裹，使用相同的细胞表面分子ACE2作为宿主受体)将用于研究竞争蛋白(如牛血清白蛋白)和噬菌体MS2存在时分子印迹gC3N4的吸附动力学和选择性。灭活效率将通过量化剩余活病毒浓度，使用Avicel覆盖的空斑分析进行评估。具体工作包括：(1)选择冠状病毒模型(如HCoV-NL63)和分子印迹的附着因子；(2)制备均一、稳定的生物分子印迹材料；(3)合成分子印迹催化剂；(4)表征目标冠状病毒粒子在分子印迹催化剂上的吸附动力学和选择性；(5)在现实条件下，比较分子印迹涂层催化剂与传统消毒方法(氯化、紫外线照射)的病毒灭活效率；以及(6)评估分子印迹催化剂项目成果的耐用性和重复使用潜力将被整合到各种课程中，包括莱斯的教师纳米环境工程(NEET)课程，该课程招收15名教师，每年接触3300多名高中生。这门课程最近扩展到了亚利桑那州立大学，也正在扩展到埃尔帕索的德克萨斯大学，从而确保在STEM教师中广泛传播这种“陷阱和突击”方法。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The virus that causes COVID-19 (i.e., SARS-CoV-2) has been found in air ducts, suggesting that it could spread around buildings via air conditioning systems. SARS-CoV-2 is also shed in stool despite patients testing negative, and thus it may reach wastewater treatment plants, where it could survive for days and be aerosolized or discharged in the effluent. In fact, there are reports that SARS-CoV-2 may spread through bathroom pipes. Although coronaviruses can be inactivated by some conventional water treatment processes, there is an urgent need for more precise viral disinfection approaches that are fast, efficient and reliable under realistic scenarios. The objective of this project is to develop a novel approach for selective adsorption and photocatalytic disinfection (i.e., trap-and-zap) of SARS-CoV-2 and other pathogenic coronaviruses. This would result in a chemical-free technology (thus avoiding harmful disinfection byproducts) with unprecedented precision and reliable efficiency to inactivate coronavirus. The driving hypothesis is that molecular imprinting of graphitic carbon nitride with common coronavirus attachment factors will enable selective virus adsorption near reactive sites, resulting in reliably high disinfection. Whereas enhancing the capacity and resiliency of wastewater disinfection and hospital air sterilization systems to protect public health against emerging infectious diseases has significant intrinsic merit, the benefits of this project are much broader. This project will enhance surface recognition of various types of coronavirus (e.g., those causing COVID-19, MERS and SARS), which will inform efforts to concentrate them and improve both precision separation (e.g., by superior sorbents) and detection limits of sensors that can be used in diagnostics and surveillance efforts. Project results will be integrated into various courses, including the NanoEnvironmental Engineering for Teachers (NEET) course at Rice, which enrolls 15 teachers that reach over 3,300 high school students annually. This course recently expanded to Arizona State University and is also being expanded to the University of Texas at El Paso, thereby ensuring wide dissemination of this “trap-and-zap” approach to STEM teachers.This project builds on a recently published, nanotechnology-enabled “trap-and-zap” approach (enhanced by molecular imprinting), to selectively adsorb antibiotic resistant genes and concentrate them near photocatalytic sites for efficient degradation (doi.org/10.1021/acs.est.9b06926). This approach will be modified to target SARS-CoV-2 and other coronavirus by imprinting molecules involved in virus attachment such as sialic acids, heparin sulfate proteoglycan, and angiotensin-converting enzyme–related carboxypeptidase (ACE2)-associated peptides onto the graphitic carbon nitride photocatalysts. When the imprinted molecule is removed (e.g., by acid washing), it leaves behind a target-specific cavity that enables selective adsorption and photocatalytic inactivation with minimum interference by background water constituents. Low pathogenic coronavirus HCoV-NL63 (which, similarly to SARS-CoV 2, is enveloped with an S spike protein and uses the same cell surface molecule ACE2 as host receptor) will be used to assess adsorption kinetics and selectivity of molecularly imprinted-gC3N4 in the presence of competing proteins (such as bovine serum albumin) and bacteriophage MS2. Inactivation efficiency will be assessed by quantifying residual viable virus concentrations, using the plaque assay with Avicel overlay. Specific tasks include to (1) select a model coronavirus (e.g., HCoV-NL63) and attachment factors for molecular imprinting; (2) prepare homogenous, stable, biomolecular materials for imprinting; (3) synthesize the molecularly-imprinted catalyst; (4) characterize adsorption kinetics and selectivity of target coronavirus particles to the molecularly-imprinted catalyst; (5) benchmark virus inactivation efficiency of the molecularly imprinted -coated catalyst against traditional disinfection methods (chlorination, ultraviolet irradiation) under realistic conditions; and (6) assess durability and reuse potential of the molecularly imprinted catalyst Project results will be integrated into various courses, including the NanoEnvironmental Engineering for Teachers (NEET) course at Rice, which enrolls 15 teachers that reach over 3,300 high school students annually. This course recently expanded to Arizona State University and is also being expanded to the University of Texas at El Paso, thereby ensuring wide dissemination of this “trap-and-zap” approach to STEM teachers.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.