New avenues of combating antibiotic resistance by targeting cryptic pockets

IF 9.1 2区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacological research Pub Date : 2024-11-03 DOI:10.1016/j.phrs.2024.107495

Yangyang Gao , Huimin Chen , Weicheng Yang , Shuang Wang , Daohong Gong , Xiao Zhang , Yuanqin Huang , Vinit Kumar , Qiuqian Huang , W.M.W.W. Kandegama , Gefei Hao

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引用次数: 0

Abstract

Antibiotic resistance is a global health concern that is rapidly spreading among human and animal pathogens. Developing novel antibiotics is one of the most significant approaches to surmount antibiotic resistance. Given the difficult in identifying novel targets, cryptic binding sites provide new pockets for compounds design to combat antibiotic resistance. However, there exists a lack of comprehensive analysis and discussion on the successful utilization of cryptic pockets in overcoming antibiotic resistance. Here, we systematically analyze the crucial role of cryptic pockets in neutralizing antibiotic resistance. First, antibiotic resistance development and associated resistance mechanisms are summarized. Then, the advantages and mechanisms of cryptic pockets for overcoming antibiotic resistance were discussed. Specific cryptic pockets in resistant proteins and successful case studies of designed inhibitors are exemplified. This review provides insight into the discovery of cryptic pockets for drug design as an approach to overcome antibiotic resistance

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针对隐匿口袋抗击抗生素耐药性的新途径。

抗生素耐药性是一个全球健康问题，正在人类和动物病原体中迅速蔓延。开发新型抗生素是克服抗生素耐药性的最重要方法之一。由于难以确定新的靶点，隐性结合位点为设计化合物以对抗抗生素耐药性提供了新的途径。然而，目前还缺乏对成功利用隐性结合位点克服抗生素耐药性的全面分析和讨论。在此，我们系统分析了隐性口袋在中和抗生素耐药性中的关键作用。首先，总结了抗生素耐药性的发展和相关的耐药性机制。然后，讨论了隐窝在克服抗生素耐药性方面的优势和机制。此外，还举例说明了耐药蛋白质中的特定隐窝以及设计抑制剂的成功案例研究。这篇综述深入探讨了发现隐窝进行药物设计作为克服抗生素耐药性的一种方法。

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来源期刊

Pharmacological research 医学-药学

CiteScore

18.70

自引率

3.20%

发文量

491

审稿时长

8 days

期刊介绍： Pharmacological Research publishes cutting-edge articles in biomedical sciences to cover a broad range of topics that move the pharmacological field forward. Pharmacological research publishes articles on molecular, biochemical, translational, and clinical research (including clinical trials); it is proud of its rapid publication of accepted papers that comprises a dedicated, fast acceptance and publication track for high profile articles.