Mechanism of Light-activated Antiviral Activity of Conjugated Polyelectrolyte Polymers and Oligomers

共轭聚电解质聚合物和低聚物的光激活抗病毒活性机制

• 批准号: 2105171
• 负责人: Eva Chi
• 金额: $ 55万
• 依托单位: University of New Mexico
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2025-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2105171&HistoricalAwards=false
• 关键词: Mechanism; Light; activated; Antiviral; Activity

NON-TECHNICAL SUMMARYThe health and economic devastation brought on by the Covid-19 pandemic underscores the urgent need to develop a multifaceted pandemic planning and response to stop viral outbreaks. This project takes a materials science and engineering approach to develop broad-spectrum antiviral materials that work against many viruses without inducing resistance. The research team has shown that a class of conjugated polymers and oligomers exhibit remarkable near-UV/visible light-activated killing of bacteriophages and the SARS-CoV-2 coronavirus that causes the Covid-19 pandemic; greater than 99.9999% viral inactivation is routinely achieved. This project focuses on elucidating the antiviral mechanism of the conjugated compounds. Propensity of the compounds to interact with and disrupt the structures and functions of several viral targets, including spike and capsid proteins, viral membrane, and RNA, will be studied using a suite of experimental techniques. Combined with computational simulations, a fundamental understanding of the interactions between the synthetic compounds with viral components that are responsible for their antiviral activity will be gained. Such insights will guide the rational design of new compounds with optimal antiviral properties to slow the spread of infections. This project will also identify virus components to target and degrade that will result in viral inactivation. Taken together, this project will contribute towards the development of highly effective and broad-spectrum antiviral materials for healthcare workers and for the public and will transform our ability to prepare for and respond to current and future outbreaks.TECHNICAL SUMMARYThe goal of this project is to gain a fundamental understanding of the intermolecular interactions between novel synthetic conjugated polyelectrolyte polymers (CPEs) and oligomers (OPEs) with various viral assemblies that give rise to their remarkable light-activated broad-spectrum antiviral activity. CPEs and OPEs have recently been shown to be highly efficient at inactivating the SARS-CoV-2 virus that causes the Covid-19 pandemic. The proposed project focuses on elucidating the antiviral mechanism of the compounds with the ultimate goal of guiding the rational design of novel materials with optimal properties. The CPEs and OPEs are charged and amphiphilic in nature, which provides them the ability to interact with and potentially disrupt the structures, and thereby functions, of multiple virial targets. Additionally, light-activated photosensitizing activity of the compounds can further contribute to their antiviral efficacy. Specifically, the propensity of CPEs and OPEs with varying backbones, chain length, side and end groups, charge density and distribution to interact with and disrupt the structures and functions of several viral macromolecular assemblies, including protein assemblies, membranes, and nucleic acids. The multidisciplinary team will use a suite of biophysical and materials characterization methods to study the interactions between CPEs and OPEs and viral targets, from molecular structural scale to macroscopic property levels, combined synergistically with closely related simulations. Comparing our findings with functional assays and antiviral activities will enable us to elucidate the toxicity mechanism and structure-function relationship of these novel synthetic antiviral materials.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.

非技术总结，共同19-19大流行带来的健康和经济灾难强调了迫切需要制定多方面的大流行计划和反应以停止病毒爆发。该项目采用材料科学和工程方法来开发广谱抗病毒材料，这些材料可与许多病毒作用，而无需诱导抗药性。研究小组表明，一类共轭聚合物和低聚物表现出极大的近紫外/可见光光激活杀害，导致COVID-19的大流行病以及SARS-COV-2冠状病毒。通常会实现大于99.9999％的病毒灭活。该项目的重点是阐明偶联化合物的抗病毒机制。化合物与多种病毒靶标的结构和功能相互作用的倾向，包括尖峰和衣壳蛋白，病毒膜和RNA，将使用一套实验技术研究。结合计算模拟，将获得对合成化合物与导致其抗病毒活性的病毒成分之间的相互作用的基本理解。这种见解将指导具有最佳抗病毒特性的新化合物的合理设计，以减缓感染的传播。该项目还将确定将导致病毒失活的靶向和降解的病毒成分。 Taken together, this project will contribute towards the development of highly effective and broad-spectrum antiviral materials for healthcare workers and for the public and will tr​​ansform our ability to prepare for and respond to current and future outbreaks.TECHNICAL SUMMARYThe goal of this project is to gain a fundamental understanding of the intermolecular interactions between novel synthetic conjugated polyelectrolyte polymers (CPEs) and oligomers (OPEs) with various viral产生其显着的光激活广谱抗病毒活性的组件。最近已证明CPE和OPE在灭活导致COVID-19大流行的SARS-COV-2病毒方面具有高效。拟议的项目着重于阐明化合物的抗病毒机制，其最终目标是指导具有最佳性能的新型材料的合理设计。本质上，CPE和OPE被充电和两亲性，这使它们具有与多种病毒靶标的结构相互作用并可能破坏结构的能力。此外，化合物的光激活光敏活性可以进一步有助于其抗病毒功效。具体而言，具有不同骨架，链长，侧面和最终组的CPE和OPES的倾向，电荷密度和分布，以与并破坏几种病毒大分子分子组件的结构和功能，包括蛋白质组件，膜，膜和核酸。多学科团队将使用一套生物物理和材料表征方法来研究CPES与OPES和病毒靶标之间的相互作用，从分子结构量表到宏观属性水平，并结合了密切相关的模拟。将我们的发现与功能测定和抗病毒活性进行比较将使我们能够阐明这些新型合成抗病毒材料的毒性机制和结构功能关系。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子和更广泛影响的评估来通过评估来获得支持的。