Center of Excellence for Encephalitic Alphavirus Therapeutics

脑炎甲病毒治疗卓越中心

• 批准号: 10563173
• 负责人: Colleen B Jonsson
• 金额: $ 302.18万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-06 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10563173
• 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; 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; Viral Physiology; Virus; Western Equine Encephalitis Virus; Wisconsin; absorption; animal model development; biothreat; design; drug candidate; efficacy study; experience; improved; in vitro Assay; in vitro activity; in vivo; inhibitor; lead candidate; lead optimization; lead series; manufacture; mouse model; multidisciplinary; pharmacologic; pre-Investigational New Drug meeting; pre-clinical; product development; programs; prophylactic; prototype; scaffold; scale up; small molecule; subcutaneous; therapeutically effective; transmission process; virology

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.

项目摘要-总体 拟议的脑炎甲病毒治疗卓越中心计划建议推进 针对委内瑞拉马脑炎病毒（VEEV）的有效小分子先导物的开发， 马脑炎病毒（EEEV）和西方马脑炎病毒（WEEV）或本文中的V/E/WEEV。的 路易斯维尔大学（UofL; Chung），威斯康星大学麦迪逊分校的科学家们 (UW田纳西大学健康科学中心（UTHSC; Jonsson，Meibohm，菲茨帕特里克， Tigabu）和德克萨斯大学医学分支在加尔维斯顿（UTMB;罗西，韦弗）提供多学科 病毒学专业知识，在ABSL-3/选择代理，小型和大型动物模型，药物 体外抗病毒化合物的化学、药代动力学和评估及其作用机制 能力的此外，该网络有一个由UTHSC（Bares）领导的经验丰富的团队来组织商业活动。 开发用于治疗V/E/WEEV的广谱抗病毒药物（Encephlavir）的计划。广阔的， 该中心的长期目标是：（1）优化喹唑啉酮铅系列，以确定那些与 对V/E/WEEV具有广谱活性的WEEV和EEEV非GLP研究的有利特征; (2)确定适合后续cGMP生产的先导原料药的放大合成;（3）进行 非临床病毒学研究，将有助于评价安全性和有效性，作用机制， 目标特异性和耐药性监测计划。拟议的多学科努力将推动这一点 通过IND赋能研究进行的领先系列。遵循严格的产品开发计划，最终目标是 该中心的目标是朝着VEEV的商业可用的预防和/或治疗性治疗迈进， EEEV和WEEV作为主要适应症。