Center of Excellence for Encephalitic Alphavirus Therapeutics

脑炎甲病毒治疗卓越中心

基本信息

批准号：
10116260
负责人：
Colleen B Jonsson
金额：
$ 510.82万
依托单位：
UNIVERSITY OF TENNESSEE HEALTH SCI CTR
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：
2019-03-06 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10116260
关键词：
Advanced Development Aerosols Alphavirus Amidines Animal Model Animals Antiviral Agents Case Fatality Rates Chemicals Chemistry Collaborations Culicidae Cyclic GMP Data Development Development Plans Discipline Disease Dose Drug Kinetics Drug resistance Eastern Equine Encephalitis Virus Elderly Encephalitis Epidemic Evaluation Excretory function Exhibits Formulation Goals Health Sciences Human In Vitro Intravenous Lead Life Medical Metabolism Modeling Monitor Oral Pharmaceutical Chemistry Pharmaceutical Preparations Pharmacologic Substance Pharmacology Polymerase Population Property Proteins Publishing Research Project Grants Resistance profile Route Safety Scientist Series Small Business Innovation Research Grant Specificity Structure Structure-Activity Relationship Tennessee Texas Therapeutic Toxic effect Toxicology Universities Vaccines Venezuelan Equine Encephalitis Virus Viral Virus Western Equine Encephalitis Virus Wisconsin absorption animal model development base biothreat design drug candidate efficacy study experience improved in vitro Assay in vitro activity in vivo inhibitor/antagonist lead candidate lead optimization lead series meetings mouse model multidisciplinary pre-clinical product development programs prophylactic prototype scaffold scale up small molecule subcutaneous therapeutically effective virology

项目摘要

Program Abstract- Overall The proposed Center of Excellence for Encephalitic Alphavirus Therapeutics program proposes to advance the development of potent small molecule leads targeting Venezuelan equine encephalitis virus (VEEV), Eastern equine encephalitis virus (EEEV) and Western equine encephalitis virus (WEEV) or V/E/WEEV herein. The collaborations among the scientists at University of Louisville (UofL; Chung), University of Wisconsin-Madison (UW; Golden, Elder), University of Tennessee Health Science Center (UTHSC; Jonsson, Meibohm, Fitzpatrick, Tigabu) and University of Texas Medical Branch at Galveston (UTMB; Rossi, Weaver) provides multidisciplinary expertise in virology with relevant expertise in ABSL-3/select agents, small and large animal models, medicinal chemistry, pharmacokinetics, and assessment of antiviral compounds in vitro with mechanism of action capabilities. Moreover, the network has an experienced team led by UTHSC (Bares) to organize the commercial plan for development of the broad-spectrum antiviral (Encephlavir) for treatment against V/E/WEEV. The broad, long-range objectives of the Center are to; (1) Optimize the lead quinazolinone series to identify those with favorable profiles for nonGLP studies with WEEV and EEEV that have broad-spectrum activity for V/E/WEEV; (2) Define scale-up synthesis of the lead drug substance suitable for later cGMP manufacturing; (3) Conduct nonclinical virology studies that will aid in the evaluation of the safety and efficacy, the mechanism of action, target specificity and drug resistance monitoring plan. The proposed multidisciplinary efforts will advance this lead series through IND-enabling studies. Following the disciplined product development plan, the ultimate goal of the Center is to move toward a commercially available prophylactic and/or therapeutic treatment for VEEV, EEEV, and WEEV as the primary indication.

程序摘要总体拟议的脑甲状腺病毒疗法卓越中心建议促进有效的小分子的发展导致针对委内瑞拉马脑炎病毒（VEEV），东部马脑炎病毒（EEEV）和西部马脑炎病毒（WEEV）或V/E/WEEV。这威斯康星大学麦迪逊分校的路易斯维尔大学（UOFL; Chung）科学家之间的合作（UW; Golden，Elder），田纳西大学健康科学中心（UTHSC； Jonsson，Meibohm，Fitzpatrick， Tigabu）和德克萨斯大学医学分公司（UTMB； Rossi，Weaver）提供多学科病毒学专业知识，具有ABSL-3/精选代理，小型和大型动物模型，药用方面的专业知识化学，药代动力学和评估抗病毒化合物的体外作用机理功能。此外，该网络拥有由UTHSC（Bares）领导的经验丰富的团队，以组织广告针对V/E/WEEV治疗的广谱抗病毒（Encephlavir）的开发计划。广泛，中心的远程目标是；（1）优化铅喹唑啉酮系列以识别那些对WEEV和EEEV进行NONGLP研究的有利概况，它们具有v/e/Weev的广谱活动；（2）定义适用于以后的CGMP制造的铅药物的扩大合成；（3）行为非临床病毒学研究将有助于评估安全性和功效，作用机理，目标特异性和耐药性监测计划。拟议的跨学科努力将推动这一点通过辅助研究进行铅序列。遵循纪律严明的产品开发计划，最终目标该中心是朝着商业可用的预防性和/或治疗治疗的VEEV迈进 EEEV，WEEV作为主要迹象。