Drug susceptibility profiles of NIAID Category A and B priority and emerging pathogens to standard of care drugs were assessed to determine susceptibility against clinical strains in addition to reference laboratory strains to establish a comparison resource for the performance of drug candidates, to define non-redundant minimal strain panels for individual species and the group of species for use in drug screening programs, and provide pharmacophore classification. Profiling of standard of care drugs against strains of each species revealed a broad spectrum of susceptibility among strains in each species with important differences between standard laboratory reference strains and strains of clinical origin. Unbiased hierarchical clustering analyses of strain susceptibilities within each species group and strains from all the species identified subsets of non-redundant strains that are able to classify the susceptibility range for each species and able to classify all the species. This analysis established a reduced targeted set of Category A and B priority pathogen strains for testing the potency of drug candidates against each species and pan-species. This approach also discriminated pharmacophore classification for each species. This information can be applied to directed screening efforts to guide the selection of drug classes for derivatization and repurposing, and advance drug candidates with the greatest potential for efficacy against NIAID Category A and B priority and emerging pathogens.

中文翻译：

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对NIAID A和B类优先级和新出现的病原体进行概要分析，以定义用于药物发现和活性药物类别的菌株组

除了参考实验室菌株外，还评估了NIAID A和B类优先级和新兴病原体对护理药物标准的药物敏感性概况，以确定对临床菌株的敏感性，从而建立了候选药物性能的比较资源，以定义非冗余的最低限度适用于药物筛选程序的单个物种和一组物种的品系，并提供药效基团分类。针对每种物种的菌株进行的护理药物标准分析表明，每种物种的菌株之间具有广泛的敏感性，标准实验室参考菌株与临床来源菌株之间存在重要差异。每个物种组内的菌株敏感性和来自所有物种的菌株的无偏等级聚类分析确定了非冗余菌株的子集，这些子集能够对每个物种的敏感性范围进行分类并能够对所有物种进行分类。这项分析建立了一套减少目标的A类和B类优先病原体菌株，以测试候选药物对每种物种和全物种的效力。这种方法还区分了每个物种的药效基团分类。该信息可用于定向筛选工作，以指导药物衍生和再利用药物类别的选择，并提高对NIAID A和B类优先级和新出现病原体具有最大潜力的候选药物。