Antiviral Drug Discovery and Development Center (AD3C)

抗病毒药物发现与开发中心（AD3C）

基本信息

批准号：
10580015
负责人：
RICHARD J. WHITLEY
金额：
$ 750万
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 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10580015
关键词：
Acceleration Address Advisory Committees Alphavirus Animal Model Animal Testing Antiviral Agents Biodistribution Biological Assay Biological Availability Biology Chemicals Collaborations Coronavirus Country Data Dengue Development Drug Kinetics Drug Screening Emerging Communicable Diseases Evaluation Evolution Flavivirus Formulation Fostering Goals Grant Human Immunity Immunology In Vitro Infection Influenza Influenza A virus Laboratories Lead Legal patent Letters Middle East Respiratory Syndrome Modeling Monitor National Institute of Allergy and Infectious Disease Nucleosides Nucleotides Outcome Pathogenesis Pharmaceutical Chemistry Pharmaceutical Preparations Pharmacologic Substance Preparation Process Property RNA Viruses Records Research Personnel Resistance Resistance development Risk Science Scientist Severe Acute Respiratory Syndrome Structure Syndrome Testing Therapeutic Therapeutic Index Toxicology Translational Research Travel Variant Venezuelan Equine Encephalitis Virus Viral Viral Genes Viral Pathogenesis Virus Virus Diseases Virus Replication West Nile virus Work ZIKA antiviral drug development chikungunya drug development drug discovery drug modification experience gene function human disease in vivo member novel novel therapeutics pharmacologic phase 1 study pre-clinical programs respiratory response small molecule therapeutics success symposium synergism therapy development translation to humans virology

项目摘要

OVERALL SUMMARY In response to RFA-AI-17-042, Centers of Excellence in Translational Research, we propose to develop small molecule therapeutics for the treatment of emerging viral infections under the umbrella of the Antiviral Drug Discovery and Development Center. We are a team of scientists experienced in virology, viral immunology, pathogenesis, medicinal chemistry, and translation to human disease. We have established four Projects – each of which addresses infections identified as high priority by the National Institute of Allergy and Infectious Diseases (NIAID). Members of several genera of RNA viruses will be studied as they are major causes of human disease, bioterrorist threats, or emerging infectious diseases. Pharmacological control of these viruses remains limited. Our Projects will focus on (1) coronaviruses that cause SARS and MERS, (2) alphaviruses including Venezuelan equine encephalitis virus and chikungunya, 3) flaviviruses including dengue, West Nile virus, and Zika and 4) influenza A virus. We will utilize lead molecules identified in recent years by AD3C to perform therapeutic proof of principle studies in animal models within the first two years of the grant. Importantly, we will additionally evaluate a limited number of novel compounds provided by our collaborators, the Emory Institute for Drug Discovery (EIDD) and Gilead Sciences in order to have back-up platforms to address the potential development of resistance. Expertise exists in the AD3C for IND enabling studies, IND preparation and filing as well as Phase I studies, should suitable candidates be identified. The projects are supported by three Cores: the Administrative Core (Core A), the Assay Core (Core B), and the Medicinal Chemistry and Lead Development Core (Core C). The organization and interaction between all Projects and Cores will be monitored by the Administrative Core. An Executive Committee (EC) will consist of all Project and Core Leads to review data on monthly conference calls, in order to provide further direction and foster project interactions. An external Scientific Advisory Committee (SAC) will be established to provide evaluation of the project progress and facilitate “Go/No-Go” decisions on a regular basis. Since its inception, AD3C has already contributed significant data to an IND filed for MERS and two patent applications for compounds with activity against chikungunya, illustrating the success of our collaborative model.

总结为了回应RFA-AI-17-042，转化研究的卓越中心，我们建议开发小型分子疗法用于治疗抗病毒药药膏下新兴病毒感染的治疗发现与发展中心。我们是一组科学家，在病毒学，病毒免疫学方面经验丰富，发病机理，药物化学和转化为人类疾病。我们已经建立了四个项目 - 每个项目其中解决了美国国家过敏和传染病研究所被确定为高度优先事项的感染疾病（NIAID）。几种RNA病毒的成员将是人类的主要原因，因为它们是人类的主要原因疾病，生物恐怖主义威胁或新兴的传染病。这些病毒的药理控制仍然存在有限的。我们的项目将重点关注（1）导致SARS和MERS的冠状病毒，（2）α病毒，包括委内瑞拉马脑炎病毒和基孔肯尼亚，3）黄病毒，包括登革热，西尼罗河病毒和 Zika和4）影响病毒。我们将利用近年来通过AD3C确定的铅分子来执行在赠款的前两年内，动物模型中原理研究的治疗证明。重要的是，我们会的另外评估了我们合作者Emory Institute提供的有限数量的新颖化合物药物发现（EIDD）和吉利德科学（Gilead Sciences），以便拥有备用平台来应对潜力阻力的发展。 AD3C中存在专业知识，以进行IND促进研究，IND准备和归档随着I期研究，应确定合适的候选人。这些项目得到了三个核心的支持：行政核心（核心A），测定核心（核心B）和药物化学和铅开发核心（核心C）。所有项目和核心之间的组织和互动将由行政核心。执行委员会（EC）将由所有项目组成，核心将导致审查有关的数据每月电话会议，以提供进一步的方向并促进项目互动。外部将建立科学咨询委员会（SAC），以评估项目进度和定期促进“执行/不执行”决定。自成立以来，AD3C已经贡献了重要向MERS提交的IND的数据和两项针对Chikungunya活性的化合物的专利申请，说明了我们的协作模型的成功。