RAPID: Investigating molecular-level responses of coronavirus under UVC irradiation

RAPID：研究冠状病毒在 UVC 照射下的分子水平反应

基本信息

批准号：
2029695
负责人：
Karl Linden
金额：
$ 20万
依托单位：
University of Colorado at Boulder
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：
2020-05-15 至 2022-04-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2029695&HistoricalAwards=false
关键词：
RAPID Investigating molecular level responses

项目摘要

Coronaviruses such as SARS-CoV1, MERS-CoV, and SARS-CoV2 (the virus responsible for COVID-19), have caused several global pandemics of respiratory diseases over the last two decades. A primary exposure pathway for coronavirus infections is through skin contact with contaminated surfaces followed by touching of facial areas. Effective and safe methods for surface disinfection against coronaviruses is urgently needed. This is particularly true in healthcare settings where reusable personal protective equipment (PPE), medical instruments, and surfaces in operating rooms need repeated disinfection. Beyond clinical settings, high-touch areas such as public transportation and commercial shops have an urgent need to stay virus-free as intervention efforts to control the pandemic are eased. Current surface disinfection methods using chemicals like bleach and alcohol can result in material corrosion and chemical residuals. A potential solution for surface disinfection is the use of ultraviolet light (UV) devices. UV light has been proven to be effective against other viruses but must be optimized to treat SARS-CoV2 and other coronaviruses because of their unique molecular structure. The study aims to understand how UV light from different sources (including newly available UVLEDs) damage the nucleic acid and proteins in SARS-CoV2 coatings. The findings will provide guidance for UV device design and operation for disinfecting contaminated surfaces, which will help in the fight against the COVID-19 global pandemic and future coronavirus-caused respiratory outbreaks. Ultraviolet light (UV) devices emitting UVC irradiation (200-280 nm) have proven to be effective for virus disinfection by damaging nucleic acids and proteins. UV exposure to non-enveloped viruses revealed that DNA/RNA damage is the primary cause for virus inactivation, with a peak efficacy around 265nm, whereas protein damage is important at wavelengths at the high (~280 nm) and low (240 nm) ends of the UV spectrum. Coronavirus, which is an enveloped, non-segmented positive-sense RNA virus, may respond to UVC irradiation differently due to its unique molecular structure. The goal of this project is to investigate inactivation kinetics and RNA and structural protein damage of coronavirus under UVC irradiation across wavelengths from 220 to 280 nm. Murine coronavirus and murine hepatitis virus (MHV) will be used as a representative coronavirus and a surrogate of human coronavirus in this project. The UVC inactivation efficiencies and kinetics of coronavirus will be determined by exposing MHV contaminated surface samples and water samples under UVC irradiation in a bench-scale collimated beam apparatus with three different UV sources: a UVLED system (emitting at 255, 265, and/or 285 nm), a KrCl excimer lamp (222 nm), and a low pressure UV lamp (254 nm). The RNA damage of MHV under UVC irradiation across wavelengths will be investigated using long range reverse transcript quantitative polymerase chain reaction and the protein damage will be assessed using peptide liquid chromatography tandem mass spectrometry. The fundamental scientific relationship between virus molecular structure and UV inactivation efficiency and mechanisms will be evaluated by comparing the UV action of coronavirus to those of nonenveloped viruses used in previous studies. These findings will lead to generation of definitive UV-disinfection kinetics of coronavirus on surfaces to inform proper operation and use of UV devices and support the engineering of new disinfection devices that will serve as urgent and effective interventions during relevant public health emergencies.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.

在过去的二十年中，诸如SARS-COV1，MERS-COV和SARS-COV2（导致Covid-19的病毒）等冠状病毒引起了几种全球呼吸系统疾病的大流行。冠状病毒感染的主要暴露途径是通过与受污染的表面接触，然后接触面部区域。迫切需要有效且安全的方法来对冠状病毒进行表面消毒。在可重复使用的个人防护设备（PPE），医疗工具和手术室中需要反复的消毒的医疗机构中，尤其如此。除临床环境之外，随着干预措施控制大流行的干预措施，公共交通和商业商店等高点式领域也迫切需要保持无病毒。当前使用漂白剂和酒精等化学物质的表面消毒方法可导致材料腐蚀和化学残留物。表面消毒的潜在解决方案是使用紫外线（UV）设备。事实证明，紫外线对其他病毒有效，但由于其独特的分子结构，必须优化以治疗SARS-COV2和其他冠状病毒。该研究旨在了解来自不同来源的紫外线（包括新近可用的紫外线）如何损害SARS-COV2涂层中的核酸和蛋白质。这些发现将为紫外线设备设计和操作提供消毒污染的表面的指导，这将有助于与19日的全球大流行和未来的冠状病毒引起的呼吸道暴发。紫外线（紫外线）设备发射UVC辐射（200-280 nm）已被证明通过破坏核酸和蛋白质对病毒消毒有效。紫外线暴露于非发育病毒表明DNA/RNA损伤是病毒失活的主要原因，峰值功效左右在265nm左右，而蛋白质损伤在高（〜280 nm）和低（240 nm）端的波长下很重要紫外线光谱。冠状病毒是一种被包膜的非细分阳性RNA病毒，由于其独特的分子结构，可能对UVC辐射有所不同。该项目的目的是研究跨220至280 nm波长的UVC照射下冠状病毒的灭活动力学和RNA和结构蛋白损伤。在该项目中，鼠冠状病毒和鼠肝炎病毒（MHV）将被用作代表性的冠状病毒和人类冠状病毒的替代物。冠状病毒的UVC灭活效率和动力学将通过在带有三种不同UV源的台式尺度准直的束机器中暴露于UVC辐射下的MHV污染的表面样品和水样在UVC辐射下进行确定：一个不同285 nm），KRCL准分子灯（222 nm）和低压UV灯（254 nm）。将使用远程逆转录定量聚合酶链反应研究MHV在UVC辐照下的RNA损伤，并将使用肽液相色谱串联质谱法评估蛋白质损伤。病毒分子结构与紫外线失活效率和机制之间的基本科学关系将通过比较冠状病毒与先前研究中使用的非发育病毒的紫外线作用来评估。这些发现将导致冠状病毒在表面上的冠状病毒的确定性紫外线感染动力学，以告知适当的操作和使用紫外线设备，并支持新的消毒设备的工程，这些设备将在相关的公共卫生紧急情况下作为紧急干预措施。 NSF的法定使命，并使用基金会的知识分子优点和更广泛的影响审查标准来评估值得支持。