Department of Molecular Genetics, University of Toronto, Toronto, Ontario, M5G 1M1, Canada.
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, M5G 1M1, Canada.
Trends Mol Med. 2024 Aug;30(8):723-735. doi: 10.1016/j.molmed.2024.04.018. Epub 2024 May 21.
Pathogenic fungi are an increasing public health concern. The emergence of antifungal resistance coupled with the scarce antifungal arsenal highlights the need for novel therapeutics. Fortunately, the past few years have witnessed breakthroughs in antifungal development. Here, we discuss pivotal interdisciplinary approaches for the discovery of novel compounds with efficacy against diverse fungal pathogens. We highlight breakthroughs in improving current antifungal scaffolds, as well as the utility of compound combinations to extend the lifespan of antifungals. Finally, we describe efforts to refine candidate chemical scaffolds by leveraging structure-guided approaches, and the use of functional genomics to expand our knowledge of druggable antifungal targets. Overall, we emphasize the importance of interdisciplinary collaborations in the endeavor to develop innovative antifungal strategies.
致病真菌是一个日益严重的公共卫生问题。抗真菌药物耐药性的出现,加上抗真菌药物的匮乏,凸显了开发新型疗法的必要性。幸运的是,过去几年在抗真菌药物的开发方面取得了突破。在这里,我们讨论了用于发现针对各种真菌病原体具有疗效的新型化合物的关键跨学科方法。我们强调了改进现有抗真菌支架的突破,以及化合物组合在延长抗真菌药物寿命方面的应用。最后,我们描述了通过利用基于结构的方法来完善候选化学支架的努力,以及利用功能基因组学来扩展可用药抗真菌靶点的知识。总的来说,我们强调了在开发创新的抗真菌策略方面开展跨学科合作的重要性。