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：
10631703
负责人：
Colleen B Jonsson
金额：
$ 93.43万
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：
2022
资助国家：
美国
起止时间：
2022-08-12 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10631703
关键词：
Advanced Development Aerosols Alphavirus Amidines Animal Model Animals Antiviral Agents Award 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 Parents 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 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

Abstract Original U19 Parent Award Program. 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) 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 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.

抽象的原始U19父母奖计划。拟议的脑静脉甲状腺病毒卓越中心 Therapeutics计划提议提高有效的小分子铅的发展委内瑞拉马脑炎病毒（VEEV），东马脑炎病毒（EEEV）和西马脑炎病毒（WEEV）或v/e/WEEV本文。大学科学家之间的合作威斯康星大学麦迪逊分校的路易斯维尔（UOFL；钟），田纳西大学健康大学科学中心（UTHSC； Jonsson，Meibohm，Fitzpatrick）和德克萨斯大学医学分支机构（UTMB； Rossi，Weaver）提供了病毒学的多学科专业知识，并具有ABSL-3/SELECT方面的相关专业知识药物，大小动物模型，药物化学，药代动力学和抗病毒评估在体外具有动作能力机理。此外，网络有一个经验丰富的团队组织广谱抗病毒（Encephlavir）的商业计划，以治疗 v/e/weev。中心的广泛，远程目标是；（1）优化喹啉唑酮系列识别具有具有广谱活动的WEEV和EEEV的NONGLP研究的有利概况的人对于v/e/weev；（2）定义适用于以后的CGMP制造的铅药物的扩大合成；（3）进行非临床病毒学研究，该研究将有助于评估安全性和功效，机制作用，目标特异性和耐药性监测计划。拟议的多学科努力将通过辅助研究推进这一铅序列。遵循纪律严明的产品开发计划，该中心的最终目标是朝着商业上可用的预防和/或治疗方法迈进对于Veev，EEEV和WEEV作为主要迹象。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Benzamidine ML336 inhibits plus and minus strand RNA synthesis of Venezuelan equine encephalitis virus without affecting host RNA production.

Benzamidine ML336 抑制委内瑞拉马脑炎病毒的正链和负链 RNA 合成，而不影响宿主 RNA 的产生。

DOI：
10.1016/j.antiviral.2019.104674
发表时间：
2020
期刊：
Antiviral research
影响因子：
7.6
作者：
Skidmore,AndrewM;Adcock,RobertS;Jonsson,ColleenB;Golden,JenniferE;Chung,Dong-Hoon
通讯作者：
Chung,Dong-Hoon

Piperazinobenzodiazepinones: New Encephalitic Alphavirus Inhibitors via Ring Expansion of 2-Dichloromethylquinazolinones.

DOI：
10.1021/acsmedchemlett.1c00539
发表时间：
2022-04-14
期刊：
ACS medicinal chemistry letters
影响因子：
4.2
作者：
Ryan MC;Kim E;Cao X;Reichard W;Ogorek TJ;Das P;Jonsson CB;Baudry J;Chung D;Golden JE
通讯作者：
Golden JE

Deep spatial profiling of Venezuelan equine encephalitis virus reveals increased genetic diversity amidst neuroinflammation and cell death during brain infection.