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Overcoming scientific and structural bottlenecks in antibacterial discovery and development

机译:克服抗菌素发现和开发中的科学和结构瓶颈

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摘要

Antibiotic resistance is becoming an increasing threat, with too few novel antibiotics coming to market to replace those lost due to resistance development. Efforts by the pharmaceutical industry to screen for and design novel antibacterials have not been successful, with several companies minimizing or closing down their antibacterial research units, leading to a loss of skills and know-how. At the same time, antibiotic innovation in academia is not filling the void due to misaligned incentive structures and lack of vital knowledge of drug discovery. The scientific and structural difficulties in discovering new antibiotics have only begun to be appreciated in the latest years. Part of the problem has been a paradigm shift within both industry and academia to focus on ‘rational’ drug development with an emphasis on single targets and high-throughput screening of large chemical libraries, which may not be suited to target bacteria. The very particular aspects of ‘targeting an organism inside another organism’ have not been given enough attention. In this paper, researcher interviews have complemented literature studies to delve deeper into the specifics of the different scientific and structural barriers, and some potential solutions are offered.
机译:抗生素耐药性正成为日益严重的威胁,很少有新型抗生素可以替代因耐药性发展而丧失的抗生素。制药行业筛选和设计新型抗菌素的努力并未取得成功,几家公司将抗菌素研究部门的人数减至最少或关闭,导致技能和专门知识的流失。同时,由于激励结构错位和缺乏重要的药物发现知识,学术界的抗生素创新并未填补空白。在最近几年中,发现新抗生素的科学和结构难题才开始被人们认识。问题的一部分是工业界和学术界的模式转变,重点是“理性”药物开发,重点是单一靶标和大型化学文库的高通量筛选,这些化学文库可能不适合目标细菌。 “针对另一生物体内的生物”的非常特殊的方面没有得到足够的重视。在本文中,研究人员访谈对文献研究进行了补充,以更深入地研究不同科学和结构性障碍的细节,并提供了一些潜在的解决方案。

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