Core B: Antiviral Drug Discovery and Development

核心B -抗病毒药物发现和开发 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， 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CoV-2（SARS 2），以及提供抗病毒药物候选人靶向病毒的潜力， 流行病核心B是进入药物开发管道的入口，作为筛选核心， 生物活性化学物质的初步发现，为早期抗病毒药物的发现提供了基础， 发展 为了在核心B中建立一个全面的筛查计划，将采用多学科方法 使用传统的超高重复率筛选（uHTS）促进平行的小分子筛选工作 在佛罗里达州斯克里普斯研究所（SRMSC），由Serravia博士领导; DNA编码化学技术（DEC-Tec） 在贝勒医学院，由Young博士领导;计算机虚拟筛查（VS）， 研究人员海德-戈登博士（加州大学伯克利分校）和阿马罗博士（加州大学圣地亚哥分校）。这个核心B计划是独一无二的， 将传统的药物HTS和虚拟筛选（VS）方法与新兴的 计算和DNA使文库筛选方法提供了一种具有成本效益的全面手段 探索药物先导化合物的新化学空间。据设想，这三个筛选组成部分， Core B（uHTS、DEC-Tec、Computational/VS）将通过反复评估周期识别电极导线系列， 使用各自的最先进的筛选技术，基于结构的设计， 通过药物化学SAR指南（Core-C）进行了细化。 核心B职责还将提供综合化合物管理服务，SRMSC将担任 从核心B研究者和核心C药物中获得的化学铅物质的中央储存库 化学努力。化合物管理将包括将化学物质数据库登记到核心A中 基于云的CDDVault并支持化学信息学和生物信息学数据的集成。化合物 管理层将提供化学品线索的储存、化学品格式化和分配，以支持正在进行的 项目和核心。 抗病毒候选药物的发现需要有效和综合的合作， 核心B研究者的经验丰富的专业知识，能够识别和分类经验证的命中系列， 通过Cores C-D支持他们的优化，并将研究人员项目纳入有前途的抗病毒药物领导者中 用于DMPK和体内动物研究。

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.