About 70% of the drugs in use are derived from natural products, either used directly or in chemically modified form. Among all possible small molecules (not greater than 5 kDa), only a few of them are biologically active. Natural product libraries may have a higher rate of finding “hits” than synthetic libraries, even with the use of fewer compounds. This is due to the complementarity between the “chemical space” of small molecules and biological macromolecules such as proteins, DNA and RNA, in addition to the three-dimensional complexity of NPs. Chemical probes are molecules which aid in the elucidation of the biological mechanisms behind the action of drugs or drug-like molecules by binding with macromolecular/cellular interaction partners. Probe development and application have been spurred by advancements in photoaffinity label synthesis, affinity chromatography, activity based protein profiling (ABPP) and instrumental methods such as cellular thermal shift assay (CETSA) and advanced/hyphenated mass spectrometry (MS) techniques, as well as genome sequencing and bioengineering technologies. In this review, we restrict ourselves to a survey of natural products (including peptides/mini-proteins and excluding antibodies), which have been applied largely in the last 5 years for the target identification of drugs/drug-like molecules used in research on infectious diseases, and the description of their mechanisms of action.

大约 70% 的使用中的药物来自天然产品，无论是直接使用还是以化学修饰的形式使用。在所有可能的小分子（不大于 5 kDa）中，只有少数具有生物活性。即使使用较少的化合物，天然产物库也可能比合成库具有更高的“命中率”。这是由于小分子的“化学空间”与蛋白质、DNA、RNA等生物大分子的互补性，以及NPs的三维复杂性。化学探针是通过与大分子/细胞相互作用伙伴结合来帮助阐明药物或类药物分子作用背后的生物学机制的分子。光亲和标记合成的进步推动了探针的开发和应用，亲和色谱、基于活性的蛋白质分析 (ABPP) 和仪器方法，如细胞热位移测定 (CETSA) 和高级/联用质谱 (MS) 技术，以及基因组测序和生物工程技术。在这篇综述中，我们仅限于对天然产物（包括肽/微型蛋白质和不包括抗体）的调查，这些产物在过去 5 年中被广泛应用于药物/类药物分子的靶标鉴定，用于研究传染病及其作用机制的描述。