Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, China.
Department of Molecular Biology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Lublin, Poland.
Br J Pharmacol. 2022 Mar;179(6):1125-1145. doi: 10.1111/bph.15724. Epub 2022 Jan 13.
Fungal infections cause serious problems in many aspects of human life, in particular infections in immunocompromised patients present serious problems. Current anti-fungal antibiotics target various metabolic pathways, predominantly the cell wall or cellular membrane metabolism. Numerous compounds are available to combat fungal infections, but their efficacy is far from satisfactory and some of them display high toxicity. The emerging antibiotic resistance represents a serious issue as well. Hence, there is a considerable need for new anti-fungal compounds with lower toxicity and higher effectiveness. One of the unique anti-fungal antibiotics is sordarin, the only known compound that acts on the fungal translational machinery per se. Sordarin inhibits protein synthesis at the elongation step of the translational cycle, acting on eukaryotic translation elongation factor 2. In this review, we deliver a robust scientific platform promoting the development of anti-fungal compounds, in particular focusing on the molecular action of sordarin.
真菌感染在人类生活的许多方面都造成严重的问题,特别是在免疫功能低下的患者中发生的感染会带来严重的问题。目前的抗真菌抗生素针对各种代谢途径,主要是细胞壁或细胞膜代谢。有许多化合物可用于对抗真菌感染,但它们的疗效远不尽如人意,其中一些还显示出很高的毒性。抗生素耐药性的出现也是一个严重的问题。因此,人们非常需要具有更低毒性和更高疗效的新型抗真菌化合物。棘白菌素是一种独特的抗真菌抗生素,它是唯一一种已知的直接作用于真菌翻译机制的化合物。棘白菌素在翻译周期的延伸步骤中抑制蛋白质合成,作用于真核翻译延伸因子 2。在这篇综述中,我们提供了一个强大的科学平台,以促进抗真菌化合物的发展,特别是侧重于棘白菌素的分子作用。