Development of Point-of-Care Diagnostics for Norovirus

描述（由申请人提供）：诺如病毒是一组非包膜单链RNA病毒，是肠胃炎爆发的主要原因，在美国每年有2100万例病例。目前的预防和控制选择有限，没有疫苗或治疗方法可用。基于抗体的诺如病毒诊断试剂盒灵敏度低，依赖于所使用的抗体。快速、准确的即时诊断包对于发现和隔离受感染人员至关重要。我们提出了一种利用合成聚糖作为捕获分子的新方法。在这项建议中，一个跨学科小组将开发快速的即时诊断方法，以灵敏地检测诺如病毒。在Specific Aim 1中，我们将使用模块化合成策略生成组织血型抗原和Lewis抗原（诺如病毒的附着因子）的合成类似物。在Specific Aim 2中，我们将使用诺如病毒毒株开发和评估基于糖聚糖的诊断平台。在Specific Aim 3中，候选诊断平台将使用来自暴发和散发胃肠道疾病病例的临床样本进行并排比较评估。实现本提案中的具体目标有望产生快速、稳健、点

DESCRIPTION (provided by applicant): Noroviruses, a group of non-enveloped single-stranded RNA viruses, are the leading cause of gastroenteritis outbreaks and account for 21 million cases in the United States annually. Current prevention and control options are limited with no vaccines or therapeutics available. Antibody-based norovirus diagnostic kits suffer from low sensitivity and are dependent on the antibody used. Rapid, accurate, point-of-care diagnostic kits are critical to detect and isolate infected personnel. We propose a novel approach by using synthetic glycans as capture molecules. In this proposal, an interdisciplinary team will develop rapid, point-of-care diagnostics for the sensitive detection of norovirus. In Specific Aim 1, we will use a modular synthetic strategy to generate synthetic analogs of histo-blood group antigens and Lewis antigens, attachment factors for norovirus. In Specific Aim 2, we will develop and evaluate glycan based diagnostic platforms using panels of norovirus strains In Specific Aim 3, candidate diagnostic platforms will be compared side-by-side evaluated using clinical samples from both outbreaks and sporadic cases of gastrointestinal illness. Accomplishing the specific aims in this proposal is expected to yield rapid, robust, point of care, user friendly diagnostics for the precise and sensitive detection of all human norovirus strains. PUBLIC HEALTH RELEVANCE: An interdisciplinary team of scientists will develop glycan-based diagnostics for norovirus, a highly infectious pathogen that causes ~50% of all gastrointestinal outbreaks in the United States. We will synthesize a library of glycans, incorporate these glycans into multiple diagnostic platforms and evaluate their performance using a comprehensive panel of archived and contemporary norovirus strains. Successful completion of these specific aims is expected to lead to the development of rapid, robust, user-friendly diagnostics for different strains of norovirus.