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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.

冠状病毒，如SARS-CoV1、MERS-CoV和SARS-CoV2（导致COVID-19的病毒），在过去二十年中导致了几次全球呼吸道疾病大流行。冠状病毒感染的主要接触途径是通过皮肤接触受污染的表面，然后接触面部区域。急需有效、安全的冠状病毒表面消毒方法。在可重复使用的个人防护装备（PPE）、医疗器械和手术室表面需要反复消毒的卫生保健环境中尤其如此。除了临床环境，随着控制大流行的干预措施放松，公共交通和商业商店等高接触区域迫切需要保持无病毒状态。目前使用漂白剂和酒精等化学物质的表面消毒方法会导致材料腐蚀和化学残留。一个潜在的表面消毒解决方案是使用紫外线（UV）设备。紫外线已被证明对其他病毒有效，但由于SARS-CoV2和其他冠状病毒的独特分子结构，必须对其进行优化才能治疗。该研究旨在了解来自不同来源的紫外线（包括新出现的uvled）如何破坏SARS-CoV2涂层中的核酸和蛋白质。这一发现将为紫外线设备的设计和操作提供指导，用于消毒受污染的表面，这将有助于抗击COVID-19全球大流行和未来冠状病毒引起的呼吸道疫情。紫外线（UV）装置发射的UVC辐射（200-280 nm）已被证明可以有效地通过破坏核酸和蛋白质来消毒病毒。暴露于非包膜病毒的紫外线下发现，DNA/RNA损伤是病毒失活的主要原因，在265nm左右达到峰值，而蛋白质损伤在紫外线光谱的高（~280 nm）和低（240 nm）波长处很重要。冠状病毒是一种包膜、非分节的正义RNA病毒，由于其独特的分子结构，可能对UVC辐射产生不同的反应。本项目的目的是研究冠状病毒在波长220 ~ 280 nm的UVC照射下的失活动力学以及RNA和结构蛋白的损伤。本项目将以鼠冠状病毒和鼠肝炎病毒（MHV）作为代表冠状病毒和人类冠状病毒的替代物。通过将MHV污染的表面样品和水样暴露在UVC照射下，确定冠状病毒的UVC失活效率和动力学，该仪器采用三种不同的紫外线源：UVLED系统（发射波长为255、265和/或285 nm）、KrCl准分子灯（222 nm）和低压紫外线灯（254 nm）。利用远程逆转录定量聚合酶链反应研究UVC照射下MHV的RNA损伤，利用多肽液相色谱串联质谱法评估MHV的蛋白质损伤。通过将冠状病毒的紫外线作用与以往研究中使用的非包膜病毒的紫外线作用进行比较，评估病毒分子结构与紫外线灭活效率和机制之间的基本科学关系。这些发现将产生明确的冠状病毒在表面上的紫外线消毒动力学，为正确操作和使用紫外线设备提供信息，并支持新型消毒设备的设计，这些设备将在相关公共卫生紧急情况下作为紧急和有效的干预措施。该奖项反映了美国国家科学基金会的法定使命，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。