Antiviral Drug Discovery and Development Center (AD3C)

抗病毒药物发现与开发中心（AD3C）

• 批准号: 10380660
• 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
• 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/10380660
• 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; antiviral drug development; 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

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.

总体汇总 为了响应RFA-AI-17-042，转化研究卓越中心，我们建议开发小型 在抗病毒药物保护伞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， 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， 其中包括国家过敏和传染病研究所确定为高度优先的感染， 疾病（NIAID）。RNA病毒的几个属的成员将被研究，因为它们是人类疾病的主要原因。 疾病、生物恐怖主义威胁或新出现的传染病。对这些病毒的药物控制仍然存在 有限公司我们的项目将集中在（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。我们将利用近年来通过AD 3C鉴定的先导分子进行 在获得资助的头两年内，在动物模型中进行治疗原理证明研究。重要的是，我们将 此外，我们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，以便有后备平台来解决潜在的 耐药性的发展。AD 3C具有IND使能研究、IND准备和归档的专业知识， 以及第一阶段的研究，以确定合适的候选人。这些项目由三个核心项目支持： 管理核心（核心A）、检测核心（核心B）以及药物化学和电极导线开发 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）将由所有项目和核心领导组成，以审查以下数据： 每月电话会议，以提供进一步的指导和促进项目互动。外部 将设立科学咨询委员会（SAC），对项目进展进行评估， 定期推动“去/不去”决策。自成立以来，AD 3C已经为 一份针对MERS的IND申请和两份针对基孔肯雅病毒活性化合物的专利申请的数据， 证明了我们合作模式的成功