Sibai Riyad E, Farahat Zainab E M, Qasem Hasnaa H, Hassan Haitham
Department of Microbiology and Biochemistry, Faculty of Science, Zagazig University Zagazig 44519 Egypt.
Department of Biochemistry, Faculty of Science, Cairo University Giza 12613 Egypt.
RSC Adv. 2025 Apr 30;15(18):14001-14029. doi: 10.1039/d5ra00016e. eCollection 2025 Apr 28.
Drug-resistant bacteria are increasingly posing an imminent existential threat, as many bacteria have developed resistance mechanisms that render most antibiotics ineffective. In the meantime, the number of newly approved antibiotics or new clinical antibacterial drug candidates is sharply declining. A key challenge is finding effective pharmacophores that can penetrate and accumulate inside bacterial cells. DNA-encoded chemical libraries (DECLs) play vital roles in accelerating hit identification and screening against various bacterial protein targets. In this review, we highlight the pivotal role of DECLs in accelerating the identification of new pharmacophores and hit compounds against drug-resistant bacteria. This review focuses on the protein targets, where DECLs have directly contributed to the rapid identification of new inhibitors. In addition, this review explores the methods used to screen DECLs against various bacterial targets and discusses the current outlook and perspectives on the role of DECLs in tackling antimicrobial resistance.
耐药细菌正日益构成迫在眉睫的生存威胁，因为许多细菌已经形成了耐药机制，使大多数抗生素失效。与此同时，新批准的抗生素或新的临床抗菌药物候选物的数量正在急剧下降。一个关键挑战是找到能够穿透并在细菌细胞内积累的有效药效基团。DNA编码化学文库（DECLs）在加速针对各种细菌蛋白靶点的命中物鉴定和筛选中发挥着至关重要的作用。在本综述中，我们强调了DECLs在加速针对耐药细菌的新药效基团和命中化合物鉴定方面的关键作用。本综述重点关注那些DECLs直接促成新抑制剂快速鉴定的蛋白靶点。此外，本综述探讨了针对各种细菌靶点筛选DECLs所使用的方法，并讨论了DECLs在应对抗菌耐药性方面的当前前景和观点。
