PDF(Pubmed)
Abstract：
Fungal-derived drugs include some of the most important medicines ever discovered, and have proved pivotal in treating chronic diseases. Not only have they saved millions of lives, but they have in some cases changed perceptions of what is medically possible. However, now the low-hanging fruit have been discovered it has become much harder to make the kind of discoveries that have characterised past eras of fungal drug discovery. This may be about to change with new commercial players entering the market aiming to apply novel genomic tools to streamline the discovery process. This review examines the discovery history of approved fungal-derived drugs, and those currently in clinical trials for chronic diseases. For key molecules, we discuss their possible ecological functions in nature and how this relates to their use in human medicine. We show how the conservation of drug receptors between fungi and humans means that metabolites intended to inhibit competitor fungi often interact with human drug receptors, sometimes with unintended benefits. We also plot the distribution of drugs, antimicrobial compounds and psychoactive mushrooms onto a fungal tree and compare their distribution to those of all fungal metabolites. Finally, we examine the phenomenon of self-resistance and how this can be used to help predict metabolite mechanism of action and aid the drug discovery process.
摘要：
真菌衍生药物包括一些有史以来发现的最重要的药物，并被证明在治疗慢性病方面至关重要。他们不仅拯救了数百万人的生命，但是在某些情况下，他们改变了对医学上可能的看法。然而,现在，低垂的果实已经被发现了，要做出那些具有真菌药物发现时代特征的发现变得更加困难。随着新的商业参与者进入市场，这可能会发生变化，旨在应用新颖的基因组工具来简化发现过程。这篇综述审查了批准的真菌衍生药物的发现历史，以及目前正在进行慢性病临床试验的人。对于关键分子，我们讨论了它们在自然界中可能的生态功能，以及这与它们在人类医学中的使用有何关系。我们展示了真菌和人类之间药物受体的保守性意味着旨在抑制竞争真菌的代谢物经常与人类药物受体相互作用，有时会带来意想不到的好处。我们还绘制了毒品的分布，将抗菌化合物和精神活性蘑菇添加到真菌树上，并将其分布与所有真菌代谢物的分布进行比较。最后,我们研究了自我抵抗现象，以及如何将其用于帮助预测代谢物的作用机制并帮助药物发现过程。
