作者
Jonathan M Stokes, Kevin Yang, Kyle Swanson, Wengong Jin, Andres Cubillos-Ruiz, Nina M Donghia, Craig R MacNair, Shawn French, Lindsey A Carfrae, Zohar Bloom-Ackermann, Victoria M Tran, Anush Chiappino-Pepe, Ahmed H Badran, Ian W Andrews, Emma J Chory, George M Church, Eric D Brown, Tommi S Jaakkola, Regina Barzilay, James J Collins
发表日期
2020/2/20
期刊
Cell
卷号
180
期号
4
页码范围
688-702. e13
出版商
Elsevier
简介
Due to the rapid emergence of antibiotic-resistant bacteria, there is a growing need to discover new antibiotics. To address this challenge, we trained a deep neural network capable of predicting molecules with antibacterial activity. We performed predictions on multiple chemical libraries and discovered a molecule from the Drug Repurposing Hub—halicin—that is structurally divergent from conventional antibiotics and displays bactericidal activity against a wide phylogenetic spectrum of pathogens including Mycobacterium tuberculosis and carbapenem-resistant Enterobacteriaceae. Halicin also effectively treated Clostridioides difficile and pan-resistant Acinetobacter baumannii infections in murine models. Additionally, from a discrete set of 23 empirically tested predictions from >107 million molecules curated from the ZINC15 database, our model identified eight antibacterial compounds that are structurally distant …
引用总数
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JM Stokes, K Yang, K Swanson, W Jin, A Cubillos-Ruiz… - Cell, 2020