孤舟蓑笠翁 (2025-06-29 09:01):
#paper 【doi】；【发表年份】2025年；【期刊】Nature；【标题】Targeting de novo purine biosynthesis for tuberculosis treatment。【内容总结】这篇研究想解决结核病治疗中药物耐药和疗程长的问题，科学家们发现了一种叫JNJ-6640的新药，它能精准打击结核菌制造嘌呤（DNA的原料）的第一步关键酶PurF。他们先筛了4924种化合物找到苗头，再改进结构让药效更强（MIC90=8.6 nM），用基因敲除、显微镜看细菌分裂、测肺里化学物质浓度等方法证明这药只杀结核菌不伤人类细胞。重要发现包括：药能让结核菌的DNA复制停工（看图3的细菌分裂动画），肺里的嘌呤原料太少救不了被药打击的细菌（表1数据），动物实验用长效针剂打两针就能减少近99%病菌。这药还能替换现有方案里毒性大的药物，可能让未来治疗更短更安全。简单说就是：找到新靶点→设计特效药→证明它管用且安全→能改进现有疗法。
Nature, 2025-6-18. DOI: 10.1038/s41586-025-09177-7
Targeting de novo purine biosynthesis for tuberculosis treatment
Dirk A. Lamprecht, Richard J. Wall, Annelies Leemans, Barry Truebody, Joke Sprangers, Patricia Fiogbe, Cadi Davies, Jennefer Wetzel, Stijn Daems, William Pearson, ... >>>
Dirk A. Lamprecht, Richard J. Wall, Annelies Leemans, Barry Truebody, Joke Sprangers, Patricia Fiogbe, Cadi Davies, Jennefer Wetzel, Stijn Daems, William Pearson, Vanessa Pillay, Samantha Saylock, M. Daniel Ricketts, Ellie Davis, Adam Huff, Tsehai Grell, Shiming Lin, Michelle Gerber, Ann Vos, John Dallow, Sam J. Willcocks, Christine Roubert, Stéphanie Sans, Amandine Desorme, Nicolas Chappat, Aurélie Ray, Mariana Pereira Moraes, Tracy Washington, Hope D’Erasmo, Pavankumar Sancheti, Melissa Everaerts, Mario Monshouwer, Jorge Esquivias, Gerald Larrouy-Maumus, Ruxandra Draghia Akli, Helen Fletcher, Alexander S. Pym, Bree B. Aldridge, Jansy P. Sarathy, Kathleen W. Clancy, Bart Stoops, Neeraj Dhar, Adrie J. C. Steyn, Paul Jackson, Clara Aguilar-Pérez, Anil Koul <<<
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