Ribosomes, which synthesize proteins, are critical organelles for the survival and growth of bacteria. About 60% of approved antibiotics discovered so far combat pathogenic bacteria by targeting ribosomes. However, several issues, such as drug resistance and toxicity, have impeded the clinical use of ribosome-targeting antibiotics. Moreover, the complexity of the bacteria ribosome structure has retarded the discovery of new ribosome-targeting agents that are considered as the key to the drug-resistance and toxicity. To deal with these challenges, efforts such as medicinal chemistry optimization, combination treatment, and new drug delivery system have been developed. But not enough, the development of structural biology and new screening methods bring powerful tools, such as cryo-electron microscopy technology, advanced computer-aided drug design, and cell-free in vitro transcription/translation systems, for the discovery of novel ribosome-targeting antibiotics. Thus, in this paper, we overview the research on different aspects of bacterial ribosomes, especially focus on discussing the challenges in the discovery of ribosome-targeting antibacterial drugs and advances made to address issues such as drug-resistance and selectivity, which, we believe, provide perspectives for the discovery of novel antibiotics.

中文翻译：

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核糖体靶向抗菌剂：进展、挑战和机遇

合成蛋白质的核糖体是细菌生存和生长的关键细胞器。迄今为止，大约 60% 的已批准抗生素通过靶向核糖体来对抗病原菌。然而，耐药性和毒性等几个问题阻碍了核糖体靶向抗生素的临床应用。此外，细菌核糖体结构的复杂性阻碍了新的核糖体靶向剂的发现，这些靶向剂被认为是耐药性和毒性的关键。为了应对这些挑战，已经开发了药物化学优化、联合治疗和新的给药系统等努力。但还不够，结构生物学的发展和新的筛选方法带来了强大的工具，如冷冻电子显微镜技术、先进的计算机辅助药物设计、和无细胞体外转录/翻译系统，用于发现新型核糖体靶向抗生素。因此，在本文中，我们概述了细菌核糖体不同方面的研究，特别是重点讨论了核糖体靶向抗菌药物发现中的挑战以及在解决耐药性和选择性等问题方面取得的进展，我们认为，为发现新型抗生素提供了前景。