RAPIDLY EMERGING ANTIVIRAL DRUG DEVELOPMENT INITIATIVE- AViDD CENTER (READDI-AC)

迅速崛起的抗病毒药物开发计划 - AViDD 中心 (READDI-AC)

• 批准号: 10513679
• 负责人: Ralph S Baric
• 金额: $ 6548.32万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-16 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10513679
• 关键词: 2019-nCoV; Address; Alphavirus; Amino Acid Motifs; Antiviral Agents; Automobile Driving; Biochemical; Biochemistry; Biological Assay; Biological Sciences; Biophysics; COVID-19; COVID-19 pandemic; Cessation of life; Chemicals; Chemistry; Chikungunya virus; Clinic; Clinical; Cold Chains; Collaborations; Communities; Computational Biology; Coronavirus; Coupling; Dangerousness; Data; Development; Disease Outbreaks; Drug Controls; Drug Design; Drug Formulations; Drug Kinetics; Drug Targeting; Drug resistance; Ebola virus; Enzymatic Biochemistry; Epidemic; Event; FDA approved; Family; Fertilization; Filovirus; Flavivirus; Future; Genomics; Goals; HIV/HCV; Home; Human; Incentives; Industrialization; Industry; Infection; Influenza; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H7N9 Subtype; Interdisciplinary Study; Investments; Lead; Leadership; Lentivirus; Methods; Middle East Respiratory Syndrome Coronavirus; Morbidity - disease rate; Norovirus; Oral; Outpatients; Peptide Hydrolases; Persons; Pharmaceutical Chemistry; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Planet Earth; Population; Prior Therapy; Private Sector; RNA Viruses; Reagent; Records; Research; Research Project Grants; Risk; SARS coronavirus; Science; Structure; Techniques; Testing; Therapeutic; Toxic effect; Training; United States; Validation; Viral; Viral Proteins; Virus; Vulnerable Populations; Zika Virus; Zoonoses; antiviral drug development; base; clinical candidate; coronavirus antiviral; crowdsourcing; design; disorder control; drug action; drug candidate; drug development; drug discovery; druggable target; enzootic; experience; global health; health economics; helicase; high risk; high throughput screening; human morbidity; human mortality; in vivo; industry partner; inhibitor; innovation; innovative technologies; medical countermeasure; member; molnupiravir; mortality; multidisciplinary; novel; nucleoside inhibitor; open data; pandemic disease; portability; preclinical development; product development; programs; public-private partnership; rational design; remdesivir; replicase; response; small molecule libraries; structural biology; therapy development; virology; virus development; zoonotic coronavirus

PROGRAM SUMMARY/ABSTRACT Emerging viruses arise suddenly and cause considerable morbidity and mortality worldwide. To prepare for current and future threats, public-private partnerships are needed to change the current reactive response platform into one that is proactive. In response to RFA-AI-21-050, the Rapidly Emerging Antiviral Drug Development Initiatives AViDD Center (READDI-AC) is an integrated public-private partnership with a renowned, interdisciplinary research team of experts, who apply cutting edge innovative technologies in virology, biochemistry, structural biology, medicinal chemistry, computational biology, structure-guided drug design and genomics to develop oral, potent, broad-spectrum family-specific antivirals for coronaviruses, flaviviruses, alphaviruses and filoviruses. To achieve these goals, the READDI-AC program includes academic leaders in basic and applied antiviral research and chemistry as well as industry leaders Janssen Pharmaceuticals N.V.(JPNV), Takeda, Chimerix Inc. and Pardes Biosciences. Our commercial partners provide an enviable track records in drug discovery and product development, and leadership in medicinal chemistry, pharmacology, drug formulation, toxicity studies and pharmacokinetics, especially critical for driving optimized leads through preIND enabling studies toward the clinic. Importantly, our industry partners also provide in kind matching contributions, access to high quality commercial chemical libraries, early hits, optimized leads, and state of the art high- throughput screens. The immediate and long-term goals of READDI-AC are to: a) validate druggable targets in conserved viral proteins, b) identify hits and leads using SAR and state of the art biochemical and enzymatic assays, c) optimize/formulate chemical probes and lead compounds as broadly acting oral compounds with activity against multiple relevant members of each emerging virus family; d) provide critical late-stage preclinical development and IND-enabling in vivo studies for two broadly active, oral drug candidates; e) promote open science sharing of unused chemical assets, chemical probes, methods, reagents and assays for innovations by crowdsourcing; f) build capacity and training in 21st century viral drug discovery and development by coupling innovative approaches in target discovery and validation with state of the art techniques, integrated workflows and novel discovery platforms for hit to lead progression and SAR optimization. READDI-AC has five Research Projects and four highly interactive cores that establish a cooperative landscape that builds leadership, expertise, response capacity and partnerships that invigorate 21st century drug development.

节目摘要/摘要 新出现的病毒突然出现，在世界范围内造成相当大的发病率和死亡率。为…做准备 当前和未来的威胁，需要公私伙伴关系来改变目前被动的反应 将平台转变为一个主动的平台。应对快速崛起的抗病毒药物RFA-AI-21-050 发展倡议AViDD中心(READDI-AC)是一个综合的公私合作伙伴关系， 将尖端创新技术应用于病毒学的跨学科专家研究团队， 生物化学、结构生物学、药物化学、计算生物学、结构导向药物设计和 基因组学开发口服、有效、广谱的针对冠状病毒、黄病毒、 甲型病毒和丝状病毒。为了实现这些目标，READDI-AC项目包括 基础和应用抗病毒研究和化学以及行业领先者扬森制药 N.V.(JPNV)、武田、Chimerix Inc.和Pardes Biosciences。我们的商业合作伙伴提供了令人羡慕的轨道 在药物发现和产品开发方面的记录，以及在药物化学、药理学、药物方面的领导 配方、毒性研究和药代动力学，特别是对通过PreIND驱动优化的导联至关重要 使临床研究成为可能。重要的是，我们的行业合作伙伴也提供了实物匹配的贡献， 访问高质量的商业化学药库、早期命中、优化的引线和最先进的 吞吐量屏幕。READDI-AC的近期和长期目标是：a)验证可用药靶点 保守的病毒蛋白，b)使用合成孔径雷达和最先进的生化和酶学识别命中和前导 分析，c)优化/制定化学探针和先导化合物，作为具有广泛作用的口服化合物 针对每个新出现的病毒家族的多个相关成员的活动；d)提供关键的晚期临床前 对两种广泛活跃的口服候选药物进行开发和体内研究；e)促进开放 科学共享未使用的化学资产、化学探针、方法、试剂和分析，以促进创新 众包；f)通过联合开展21世纪病毒药物发现和开发方面的能力建设和培训 在目标发现和验证方面采用创新方法，采用最先进的技术、集成的工作流程 以及新颖的发现平台，用于HIT引领进步和SAR优化。Readdi-AC有五项研究 项目和四个高度互动的核心，建立了一个建立领导力、专业知识、 为21世纪药物开发注入活力的应对能力和伙伴关系。