Biomimetic Redox Chemistry for Antiviral Application

第1部分：非技术概述活性氧类(ROS)可用于广泛的病原体消毒，如病毒、细菌和真菌。ROS是一种很有吸引力的消毒剂，因为它能分解成无毒的降解产物(水和氧气)。然而，ROS是高度活性的，对储存和运输可能是危险的。该项目旨在利用贻贝黏附蛋白中发现的一种独特的化学物质来创造一种便携式生物材料，这种材料可以被激活以产生ROS。产生的ROS的抗病毒能力将被测试以对抗不同性质和不同抗药性水平的病毒。生物材料本身不含ROS，仅通过简单的水合过程被激活以产生ROS。所提出的仿生材料可能被用作便携式、轻量的消毒剂来预防病毒感染。拟议的研究将吸引本科生和研究生，以及代表不足的社区大学学生，参与涉及聚合物材料、仿生化学和抗病毒研究的跨学科研究。此外，调查人员将开发一种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，向高中生介绍与将生物材料用作药物载体有关的动手活动。第2部分：技术总结拟议的工作旨在获取贻贝粘附性蛋白中发现的一种独特的还原-氧化化学的副产品，用于抗病毒应用。聚合物用粘合剂分子邻苯二酚功能化，在自氧化过程中会产生过氧化氢。为了增强含儿茶酚材料的抗病毒能力，将调整聚合物的结构和组成以及邻苯二酚的反应活性，以创建优化的聚合物系统，以产生基于自由基的有效ROS，如超氧阴离子和羟基自由基。将探索产生的ROS灭活包膜和非包膜病毒以及疱疹病毒的能力。这项建议的结果将使人们更好地了解灭活具有不同杀生剂抗性特性和水平的不同类型病毒所需的ROS剂量、持续时间和类型。当材料在pH值为中性的水溶液中水合时，按需产生ROS。这个过程包括通过邻苯二酚部分的氧化，将溶液中的分子氧转化为ROS。这种方法与其他现有的方法有很大的不同，这些方法含有ROS，需要外部提供的化学反应物，或者需要外部能源来产生ROS。该材料不包含用于存储反应性ROS的储存库，这极大地简化了它的存储和运输方式。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。

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.