Antiviral Drug Discovery and Development Center (AD3C)

总体总结 为了响应RFA-AI-17-042，翻译研究英才中心，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 探索与发展中心。我们是一个在病毒学、病毒免疫学方面经验丰富的科学家团队， 发病机制、药物化学和对人类疾病的转化。我们已经建立了四个项目-每个项目 其中涉及被国家过敏和传染病研究所确定为高度优先的感染 疾病(NIAID)。我们将研究几种核糖核酸病毒属的成员，因为它们是人类 疾病、生物恐怖威胁或新出现的传染病。这些病毒的药理控制仍然存在 有限的。我们的项目将集中于(1)导致SARS和MERS的冠状病毒，(2)包括 委内瑞拉马脑炎病毒和基孔肯雅病毒，3)黄病毒，包括登革热、西尼罗河病毒和 寨卡病毒和甲型流感病毒。我们将利用AD3C近年来确定的铅分子来执行 在拨款的头两年内，在动物模型中进行治疗原理研究的证明。重要的是，我们会 此外，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化合物 药物发现(EIDD)和吉利德科学公司，以便有后备平台来应对潜在的 抗药性的发展。AD3C在IND支持研究、IND准备和归档方面拥有专业知识，如 以及第一阶段的研究，如果确定合适的候选人。这些项目得到三个核心的支持： 管理核心(核心A)、分析核心(核心B)以及药物化学和铅开发 核心(核心C)。所有项目和核心之间的组织和互动将由 管理核心。执行委员会(EC)将由所有项目和核心领导组成，以审查以下数据 每月召开电话会议，以便提供进一步指导和促进项目互动。一个外部的 将成立科学咨询委员会(SAC)，以评估项目进展和 促进定期做出“去/不去”的决定。自成立以来，AD3C已经做出了重大贡献 为MERS提交的IND数据和两项具有抗基孔肯雅热活性的化合物的专利申请， 说明了我们的协作模式的成功。

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.