Biomimetic Redox Chemistry for Antiviral Application

第一部分： 活性氧物质（ROS）可用于对多种病原体进行消毒，例如病毒、细菌和真菌。ROS是一种有吸引力的消毒剂，因为它分解成无毒的降解产物（水和氧气）。然而，ROS是高度反应性的，并且对于储存和运输可能是危险的。该项目旨在利用贻贝粘附蛋白中发现的独特化学物质来创建可激活以产生ROS的便携式生物材料。所产生的ROS的抗病毒能力将针对具有不同性质和化学抗性水平的不同病毒进行测试。生物材料本身不含ROS，仅通过简单的水合过程活化产生ROS。所提出的仿生材料可以潜在地用作用于预防病毒感染的便携式、轻质消毒剂。拟议的研究将吸引本科生和研究生，以及代表性不足的社区学院学生，在跨学科研究，涉及聚合物材料，仿生化学和抗病毒研究。此外，研究人员将开发一个新的聚合物生物材料模块，作为密歇根理工大学暑期青年计划的一部分，向高中生介绍与使用生物材料作为药物载体相关的实践活动。第二部分： 技术概述所提出的工作旨在收获贻贝粘附蛋白中发现的用于抗病毒应用的独特的还原-氧化化学的副产物。聚合物用粘合剂分子儿茶酚官能化，儿茶酚在自氧化过程中产生过氧化氢。为了增强含儿茶酚材料的抗病毒能力，聚合物结构和组成以及儿茶酚的反应性将被调整以产生被优化以产生有效的基于自由基的ROS（例如超氧阴离子和羟基自由基）的聚合物系统。将探索所产生的ROS抑制包膜和非包膜病毒以及疱疹病毒的能力。该提案的结果将使人们更好地了解ROS的剂量、持续时间和类型，以杀灭具有不同性质和抗生物剂抗性水平的不同类型的病毒。当材料在中性pH的水溶液中水合时，按需产生ROS。该过程涉及通过儿茶酚部分的氧化将溶液中的分子氧转化为ROS。这种方法与含有ROS、需要外部提供的化学反应物或需要外部能源来产生ROS的其他现有方法截然不同。该材料不包含用于储存活性氧的储存器，这大大简化了其储存和运输的方式。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。

PART 1: NON-TECHNICAL SUMMARY Reactive oxygen species (ROS) can be used to disinfect a wide range of pathogens, such as viruses, bacteria, and fungi. ROS is an attractive disinfectant as it decomposes into non-toxic degradation products (water and oxygen). However, ROS is highly reactive and can be hazardous to store and transport. This project aims at utilizing a unique chemistry found in mussel adhesive proteins to create a portable biomaterial that can be activated to generate ROS. The antiviral capability of the generated ROS will be tested against different viruses with varying properties and levels of chemical resistance. The biomaterial itself does not contain ROS and is only activated to generate ROS by a simple hydration process. The proposed biomimetic material can potentially be used as a portable, light-weight disinfectant for preventing viral infection. The proposed research will engage undergraduate and graduate students, as well as underrepresented community college students, in interdisciplinary research involving polymeric materials, biomimetic chemistry, and antiviral research. Additionally, investigators will develop a new polymeric biomaterials module as part of the Michigan Technology University Summer Youth Program to introduce high school students in hands-on activities related to the use of biomaterials as a drug carrier. PART 2: TECHNICAL SUMMARYThe proposed work aims at harvesting the byproduct of a unique reduction-oxidation chemistry found in mussel adhesive proteins for antiviral application. Polymers are functionalized with the adhesive molecule, catechol, which generate hydrogen peroxide during autoxidation. To enhance the antiviral capability of catechol-containing materials, polymer architecture and composition, as well as the reactivity of catechol will be tuned to create polymer systems that are optimized to generate potent radical-based ROS, such as superoxide anion and hydroxyl radical. The ability for the generated ROS to inactivate both enveloped and non-enveloped viruses as well as a herpes virus will be explored. Results from this proposal will provide a greater understanding on the dose, duration, and type of ROS needed to inactivate different types of viruses with varying properties and levels of biocide resistance. ROS is generated on-demand when the material is hydrated in an aqueous solution with neutral pH. This process involves the conversion of molecular oxygen in the solution to ROS, through the oxidation of the catechol moiety. This approach is drastically different from other existing approaches that contain ROS, require externally provided chemical reactants, or require external energy sources to generate ROS. The material does not contain a reservoir for storing the reactive ROS, which greatly simplifies how it could be stored and transported.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.