Core B: Antiviral Drug Discovery and Development

核心B-抗病毒药物的发现和开发 摘要 中西部AViDD中心由多学科团队组成，由高度集成的核心支持，以 确定和开发口服药物，以应对严重急性呼吸系统疾病的直接威胁 综合征冠状病毒-2(SARS2)，以及提供针对病毒的抗病毒候选药物 大流行。Core-B是进入药物开发流水线的入口，是 生物活性化学物质的初步发现，为早期抗病毒药物的发现和开发奠定了基础 发展。 为了在Core-B中建立一个全面的筛查计划，将采用多学科方法 使用传统的超高通量筛选(UHTS)促进并行小分子筛选工作 在斯克里普斯研究-佛罗里达州(SRMSC)，在斯坎维娅博士的领导下；DNA编码化学技术(DEC-Tec) 在贝勒医学院，在杨博士的指导下；在电子计算机虚拟筛选(VS)的计算下 研究人员Head-Gordon博士(加州大学伯克利分校)和Amaro博士(UCSD)。这个Core-B计划是独一无二的 将传统药物HTS和虚拟筛选(VS)方法与新兴技术相结合的方法 计算型和DNA使能文库筛选方法提供了一种经济有效和全面的手段 探索药物先导的新化学空间。据设想，三个筛选组件将 核心B(uHTS、DEC-Tec、计算/VS)将通过评估和 使用各自最先进的筛选技术、基于结构的设计和 在药物化学搜救指南(Core-C)的指导下实现了精细化。 核心-B职责还将提供综合复合管理服务，其中SRMSC将充当 从Core-B调查人员和Core-C Medical获得的化学铅物质的中央存储库 化学方面的努力。化合物管理将包括将化学物质的数据库注册到Core-A 基于云的CDDVault以及对化学信息和生物信息数据集成的支持。化合物 管理层将提供化学线索的存储、化学格式化和分配，以提供持续支持 项目和核心。 抗病毒候选药物的发现需要有效和集成的合作，利用高度 CORE-B调查人员的经验丰富的专业知识，能够识别和分类经过验证的热门系列剧和 通过核心C-D支持他们的优化，并将研究人员计划到有希望的抗病毒药物线索 用于DMPK和活体动物研究。

Core B – Antiviral Drug Discovery and Development ABSTRACT The Midwest AViDD center is comprised of multidisciplinary teams supported by highly integrated cores to identify and develop orally available drugs to address the immediate threat of Severe Acute Respiratory Syndrome CoV-2 (SARS2), as well as provide antiviral drug candidates targeting viruses with the potential for pandemics. Core-B is the entry portal into the drug development pipeline, serving as the screening core for the initial discovery of bioactive chemical matter that provides the basis for early antiviral drug discovery and its development. To establish a comprehensive screening program within Core-B, a multidisciplinary approach will be employed to facilitate parallel small molecule screening efforts using traditional ultra-High Throughput Screening (uHTS) at Scripps Research-Florida (SRMSC) under Dr. Scampavia; DNA-Encoded Chemistry Technology (DEC-Tec) at the Baylor School of Medicine under Dr. Young; and Computational in silico Virtual Screening (VS) under investigators Dr. Head-Gordon (UC Berkeley) and Dr. Amaro (UCSD). This Core-B program is unique in its approach having integrated traditional pharmaceutical HTS and Virtual Screening (VS) methods with emerging Computational and DNA-enable library screening methods to provide a cost-effective and comprehensive means of exploration into novel chemical space for drug leads. It is envisioned that the three screening components to Core B (uHTS, DEC-Tec, Computational/VS) will identify lead series through iterative cycles of evaluation and refinement using their respective state-of-the-art screening technologies, structure-based design, and with refinement made possible with medicinal chemistry SAR guidance (Core-C). Core-B duties will also provide integrated compound management services, where SRMSC will serve as the central repository of acquired chemical lead matter derived from its Core-B investigators and Core-C medicinal chemistry efforts. Compound management will include database registration of chemical matter into Core-A cloud-based CDDVault and support for the integration of cheminformatic and bioinformatic data. Compound management will provide storage, chemical formatting, and allocation of chemical leads to support ongoing projects and Cores. The discovery of antiviral candidates requires effective and integrated collaborations leveraging the highly experienced expertise of core-B investigators to enable the identification and triage of validated hit series and support their optimization through Cores C-D and project investigators into promising antiviral drug leads suitable for DMPK and in vivo animal studies.