Project 3 - Flavivirus - UTMB

项目 3 - 黄病毒 - UTMB

基本信息

批准号：
10115600
负责人：
PEI-YONG SHI
金额：
$ 92.66万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-07 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10115600
关键词：
Academia Active Sites Address Advisory Committees Algorithms Alphavirus Antiviral Agents Antiviral Therapy Binding Biochemical Biological Assay Biology Capsid Capsid Proteins Cell Culture Techniques Cells Collection Combined Modality Therapy Complex Coronavirus Crystallization Culicidae Dengue Infection Dengue Virus Development Diamond Disease Outbreaks Drug Kinetics Epidemic Exhibits FDA approved Family member Flavivirus Flavivirus Infections Foundations Funding Future Goals HIV/HCV Health Sciences Hepatitis C virus Human Immune Evasion In Vitro Industry Infection Institutes Japanese encephalitis virus Jordan Medical Modeling Mus Nucleosides Nucleotides Oregon Pathogenesis Pathogenicity Patients Pharmaceutical Chemistry Pharmaceutical Preparations Phosphotransferases Polymerase Prodrugs Proteins Public Health RNA Viruses RNA-Directed RNA Polymerase Regimen Research Research Personnel Resistance Science Solubility Structure Testing Texas Tick-Borne Encephalitis Virus Universities Vaccines Variant Viral Virus Virus Diseases Washington West Nile virus Yellow fever virus Zika Virus animal efficacy aqueous base clinical candidate clinical implementation combat design drug candidate drug development drug discovery efficacy testing fitness human pathogen improved in vivo inhibitor/antagonist lead optimization mosquito-borne mouse model nonhuman primate novel nucleoside triphosphate optimal treatments pathogenic virus phosphonate phosphoramidate pre-clinical preclinical development prevent protein function public health priorities targeted agent therapeutic evaluation viral RNA

项目摘要

Summary Many flaviviruses are significant human pathogens, among which dengue virus is the most important mosquito-borne viral pathogen with over 390 million infections per year. Apart from dengue virus, West Nile virus, yellow fever virus, Japanese encephalitis virus, tick-borne encephalitis virus, and recently Zika virus cause global outbreaks and epidemics, posing constant threats to public health. No FDA-approved antiviral drug is currently available to treat any flavivirus infection, and vaccines are lacking against several family members. Thus, the development of flavivirus antiviral therapy is a public health priority. The goal of this proposal is to develop direct antiviral agents (DAAs) for flavivirus therapy. We will pursue three Specific Aims to develop flavivirus DAAs. Aim 1. Develop preclinical DAAs targeting flavivirus capsid and NS4B protein. Aim 2. Identify novel Nuc DAAs with pan-flavivirus activity. Aim 3. Evaluate combination therapy directed against flavivirus infection. We will deliver the proposed milestones by combining the cutting-edge biology from academia and drug discovery acumen from industry with clear go/no-go criteria.

概括许多黄病毒是重要的人类病原体，其中登革热病毒是最重要的重要的蚊媒病毒病原体，每年感染人数超过 3.9 亿。除了登革热病毒、西尼罗河病毒、黄热病病毒、日本脑炎病毒、蜱传病毒脑炎病毒和最近的寨卡病毒导致全球爆发和流行，构成持续的威胁对公共健康的威胁。目前尚无 FDA 批准的抗病毒药物可用于治疗任何黄病毒感染，并且缺乏针对几名家庭成员的疫苗。因此，发展黄病毒抗病毒治疗是公共卫生的优先事项。该提案的目标是开发用于黄病毒治疗的直接抗病毒药物（DAA）。我们将追求三个具体目标开发黄病毒 DAA。目标 1. 开发针对黄病毒衣壳和 NS4B 的临床前 DAA 蛋白质。目标 2. 鉴定具有泛黄病毒活性的新型 Nuc DAA。目标 3. 评估组合针对黄病毒感染的治疗。我们将通过结合以下方式实现拟议的里程碑来自学术界的尖端生物学和来自工业界的药物发现敏锐度，具有明确的通过/不通过标准。