Receptor Mimics for Rapid Detection, Typing, and Susceptibility Testing of Influe

用于流感快速检测、分型和药敏测试的受体模拟物

• 批准号: 8509585
• 负责人: Suri Saranathan Iyer
• 金额: $ 35.76万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-15 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8509585
• 关键词: Accounting; Antiviral Agents; Antiviral resistance; Architecture; Basic Science; Binding; Biological Assay; Biosensor; Birds; Cessation of life; Clinical; Data; Detection; Development; Diagnosis; Diagnostic; Discrimination; Equipment; Evaluation; Exposure to; Feces; Fingerprint; Generations; Genomics; GlaxoSmithKline brand of zanamivir; Glycosides; Goals; Grapes; HN Protein; Hemagglutinin; Hospitalization; Human; Human Resources; In Vitro; Influenza; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H5N1 Subtype; Juice; Laboratories; Lead; Libraries; Methods; Milk; Neuraminidase; One-Step dentin bonding system; Oseltamivir; Patients; Pattern Recognition; Performance; Polysaccharides; Positioning Attribute; Predisposition; Reporting; Research; Resistance; Sampling; Scientist; Solutions; Structure; Study Section; Surface; Technology; Testing; Time; Toxin; Training; Viral; Viral Drug Resistance; Virion; Virus; World Health Organization; Writing; base; burden of illness; design; fight against; flu; influenzavirus; multidisciplinary; novel; novel diagnostics; pandemic disease; pathogen; point of care; point-of-care diagnostics; rapid detection; receptor; research and development; resistance mutation; seasonal influenza; swine flu; user-friendly

DESCRIPTION (provided by applicant): Disease burden due to influenza is significant. The 2009 H1N1 pandemic is unfolding as this proposal is being written. As of August 23, 2009, over 209,438 laboratory-confirmed cases of 2009 H1N1 influenza viruses with at least 2,185 deaths have been reported by the World Health Organization. Rapid, accurate, point-of-care detection kits that possess the capability to test for susceptibility of the virus to current antivirals are critical in our fight against this deadly virus. The objective of this proposal is to develop novel glycan based diagnostic platforms that target the viral glycoproteins, Hemagglutinin (HA) and Neuraminidase (NA), which are abundant (~50 copies of tetrameric NA and 300 copies of trimeric HA) on the surface of the virion. The rationale for this proposal is that a well designed glycan microarray platform will yield a "fingerprint pattern of recognition" on exposure to the virus. The novelty of this proposal is that susceptibility to Tamiflu(r) and Relenza(r), can be rapidly evaluated without the time consuming need to identify and characterize an emerging strain. In Specific Aim 1, we will generate a library of glycans to capture and assess antiviral susceptibility of influenza. In Specific Aim 2, we will develop different diagnostic platforms to capture and type influenza strains. We will also develop tests to determine sensitivity or resistance to antiviral agents. These tests are especially important since there is currently no method to rapidly detect and assess antiviral susceptibility before the genomic sequence for antiviral resistance mutations has been determined. In Specific Aim 3, we will evaluate the different platforms using clinical samples. Specifically, we will examine the robustness, sensitivity, and selectivity of the diagnostic platforms using clinical samples isolated from infected patients and assess antiviral susceptibility. Accomplishing the specific aims in this proposal is expected to yield rapid, robust, point of care, user friendly diagnostics for the precise detection and differentiation of different influenza strains.

描述（由申请人提供）：由于流感引起的疾病负担很大。随着该提议的编写，2009 H1N1大流行正在展开。截至2009年8月23日，世界卫生组织报告了2009年H1N1流感病毒的2009年H1N1流感病毒的209,438例案例，世界卫生组织已经报告了至少2185例死亡。具有测试病毒对当前抗病毒药敏感性的能力的快速，准确，护理检测套件对于我们与这种致命病毒的斗争至关重要。该提案的目的是开发基于聚糖的诊断平台，以靶向病毒糖蛋白，血凝集素（HA）和神经氨酸酶（Na），它们是丰富的（〜50个四聚体Na和300份副本的三聚体HA拷贝）病毒体。该提案的理由是，设计良好的聚糖微阵列平台将在暴露于病毒时产生“指纹识别模式”。该提案的新颖性是，可以快速评估对塔米夫鲁（R）和Relenza（R）（R）的敏感性，而无需花费时间来识别和表征新兴菌株。在特定目标1中，我们将生成一个聚糖库，以捕获和评估流感的抗病毒药易感性。在特定目标2中，我们将开发不同的诊断平台来捕获和键入流感菌株。我们还将开发测试以确定对抗病毒药的敏感性或抗性。这些测试尤其重要，因为目前尚未确定抗病毒药抗性突变基因组序列之前快速检测和评估抗病毒敏感性。在特定的目标3中，我们将使用临床样本评估不同的平台。具体而言，我们将使用从感染患者中分离出来的临床样本来检查诊断平台的鲁棒性，灵敏度和选择性，并评估抗病毒药易感性。预计该提案中的具体目标有望产生快速，健壮，护理点，用户友好的诊断，以确切检测和区分不同的流感菌株。