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：
9888306
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 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9888306
关键词：
Address Advisory Committees Alphavirus Animal Model Animal Testing Antiviral Agents Back 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 Institutes 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 Pharmacology Preparation Process Property RNA Viruses Records Research Personnel Resistance Resistance development Risk Science Scientist Severe Acute Respiratory Syndrome Structure Testing Therapeutic Therapeutic Index Toxicology Translational Research Travel Variant Venezuelan Equine Encephalitis Virus Viral Viral Pathogenesis Virus Virus Diseases Virus Replication West Nile virus Work ZIKA chikungunya drug development drug discovery drug modification experience gene function human disease in vivo member novel novel therapeutics phase 1 study pre-clinical programs 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.

总体总结为了响应 RFA-AI-17-042（转化研究卓越中心），我们建议开发小型在抗病毒药物的保护下治疗新出现的病毒感染的分子疗法我们是一支在病毒学、病毒免疫学方面经验丰富的科学家团队。我们已经建立了四个项目——每个项目。其中解决了国家过敏和传染病研究所确定为高度优先的感染问题疾病 (NIAID) 将研究几个 RNA 病毒属的成员，因为它们是人类的主要原因。疾病、生物恐怖威胁或新出现的传染病仍然需要对这些病毒进行药物控制。我们的项目将重点关注 (1) 引起 SARS 和 MERS 的冠状病毒，(2) 甲病毒，包括委内瑞拉马脑炎病毒和基孔肯雅热，3) 黄病毒，包括登革热、西尼罗河病毒和寨卡病毒和4）甲型流感病毒我们将利用AD3C近年来鉴定的先导分子来进行研究。重要的是，我们将在资助的头两年内进行动物治疗模型的原理研究证明。另外还评估了我们的合作者埃默里研究所提供的有限数量的新型化合物药物发现 (EIDD) 和吉利德科学公司，以便拥有后备平台来解决潜在问题 AD3C 拥有用于 IND 研究、IND 准备和备案的专业知识。以及第一阶段研究，如果确定了合适的候选人，这些项目将得到三个核心的支持：管理核心（核心 A）、检测核心（核心 B）以及药物化学和先导化合物开发核心（核心 C）。所有项目和核心之间的组织和互动将由执行委员会 (EC) 将由所有项目和核心负责人组成，负责审查相关数据。每月举行电话会议，以提供进一步的指导并促进外部互动。将成立科学咨询委员会（SAC），对项目进展进行评估并自成立以来，AD3C 已经做出了重大贡献。针对 MERS 提交的 IND 数据以及两项具有抗基孔肯雅热活性的化合物专利申请，说明了我们协作模式的成功。