FACS ANALYSIS OF ANTIVIRAL DRUGS ON HCMV REPLICATION

抗病毒药物对 HCMV 复制的 FACS 分析

• 批准号: 2873489
• 负责人: James McSharry
• 金额: $ 7.75万
• 依托单位: ALBANY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2873489
• 关键词: antiviral agents; antiviral antibody; clinical research; cytomegalovirus; drug screening /evaluation; flow cytometry; fluorescent dye /probe; human subject; technology /technique development; virus antigen; virus replication

DESCRIPTION (Adapted from applicant's abstract): The long term goals of this project are 1) to validate a flow cytometry drug susceptibility assay for use with antiviral compounds effective against human cytomegalovirus; and 2) to demonstrate the feasibility of using fluoroochrome labeled monoclonal antibodies to viral antigens and flow cytometry to begin to determine the mode of action of these antiviral compounds. Human cytomegalovirus (HCMV) infection is a major cause of morbidity and mortality in immunocompromised patients. There are three licensed antiviral drugs for use for treatment of HCMV associated retinitis in this patient population and a number of novel antiviral compounds are under development. The current procedures for determining drug susceptibility of HCMV clinical isolates are time consuming, labor intensive, and subjective. Mode of action studies are also labor intensive and time consuming. There is a need for better methods for measuring the susceptibility of HCMV chemical isolates to antiviral drugs and their mode(s) of action. Novel antiviral drugs effective against HCMV infection have been obtained from pharmaceutical companies. The susceptibilities of drug sensitive and drug resistant HCMV laboratory strains and clinical isolates to these antiviral drugs will be assessed using this flow cytometry drug susceptibility assay. Fluorochrome labeled monoclonal antibodies to immediate early (IE), early and late HCMV antigens, the DNA stain propidium iodide , and flow cytometry also will be used to begin to elucidate the mode(s) of action of these novel antiviral compounds. The introduction of flow cytometry technology for use in antiviral drug research will speed the discovery of more effective and safer drugs effective against HCMV. Extension of this flow cytometry technology for drug susceptibility and mode of action studies to antiviral drugs effective against other viruses will eventually make this a broadly used technique in antiviral research.

描述（改编自申请人的摘要）：本项目的长期目标 项目是1）验证流式细胞术药物敏感性测定的使用 与有效对抗人巨细胞病毒的抗病毒化合物;和2） 证明了使用荧光染料标记的单克隆抗体的可行性， 病毒抗原抗体和流式细胞术开始，以确定模式 这些抗病毒化合物的作用。人巨细胞病毒（HCMV）感染 是免疫功能低下患者发病和死亡的主要原因。 有三种许可的抗病毒药物用于治疗HCMV 与此相关的视网膜炎患者人群和一些新的抗病毒药物 化合物正在开发中。目前用于确定药物的程序 HCMV临床分离株的易感性是耗时的，劳动密集的， 也很主观行动模式研究也是劳动密集型和时间 消耗。需要更好的方法来测量敏感性 HCMV化学分离株对抗病毒药物及其作用方式的影响。小说 有效对抗HCMV感染的抗病毒药物已经从 制药公司。药物敏感性和药物敏感性 对这些抗病毒药物具有抗性的HCMV实验室菌株和临床分离株 将使用该流式细胞术药物敏感性测定来评估药物。 荧光染料标记的单克隆抗体，以立即早期（IE），早期和 晚期HCMV抗原、DNA染色碘化丙啶和流式细胞术也 将用于开始阐明这些小说的行动模式 抗病毒化合物。流式细胞术技术的引入， 抗病毒药物研究将加速发现更有效、更安全的 抗HCMV的有效药物这种流式细胞术技术的扩展， 药物敏感性和抗病毒药物有效作用方式研究 对抗其他病毒最终将使其成为一种广泛使用的技术， 抗病毒研究