体内
病毒复制
细胞生物学
化学
环胺
病毒学
病毒
抄写(语言学)
药品
生物
药理学
信号转导
遗传学
语言学
哲学
刺猬
作者
Jennifer Risso-Ballester,Marie Galloux,Jingjing Cao,Ronan Le Goffic,Fortune Hontonnou,Aude Jobart-Malfait,Aurore Desquesnes,Svenja M. Sake,Sibylle Haid,Miaomiao Du,Xiumei Zhang,Huanyun Zhang,Zhaoguo Wang,Vincent Rincheval,Youming Zhang,Thomas Pietschmann,Jean-François Éléouët,Marie‐Anne Rameix‐Welti,Ralf Altmeyer
出处
期刊:Nature
[Springer Nature]
日期:2021-07-07
卷期号:595 (7868): 596-599
被引量:132
标识
DOI:10.1038/s41586-021-03703-z
摘要
Biomolecular condensates have emerged as an important subcellular organizing principle1. Replication of many viruses, including human respiratory syncytial virus (RSV), occurs in virus-induced compartments called inclusion bodies (IBs) or viroplasm2,3. IBs of negative-strand RNA viruses were recently shown to be biomolecular condensates that form through phase separation4,5. Here we report that the steroidal alkaloid cyclopamine and its chemical analogue A3E inhibit RSV replication by disorganizing and hardening IB condensates. The actions of cyclopamine and A3E were blocked by a point mutation in the RSV transcription factor M2-1. IB disorganization occurred within minutes, which suggests that these molecules directly act on the liquid properties of the IBs. A3E and cyclopamine inhibit RSV in the lungs of infected mice and are condensate-targeting drug-like small molecules that have in vivo activity. Our data show that condensate-hardening drugs may enable the pharmacological modulation of not only many previously undruggable targets in viral replication but also transcription factors at cancer-driving super-enhancers6.
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