Details

Autor(en) / Beteiligte

• Yuan, Shuofeng
• Chu, Hin
• Chan, Jasper Fuk-Woo
• Ye, Zi-Wei
• Wen, Lei
• Yan, Bingpeng
• Lai, Pok-Man
• Tee, Kah-Meng
• Huang, Jingjing
• Chen, Dongdong
• Li, Cun
• Zhao, Xiaoyu
• Yang, Dong
• Chiu, Man Chun
• Yip, Cyril
• Poon, Vincent Kwok-Man
• Chan, Chris Chung-Sing
• Sze, Kong-Hung
• Zhou, Jie
• Chan, Ivy Hau-Yee
• Kok, Kin-Hang
• To, Kelvin Kai-Wang
• Kao, Richard Yi-Tsun
• Lau, Johnson Yiu-Nam
• Jin, Dong-Yan
• Perlman, Stanley
• Yuen, Kwok-Yung

Titel

SREBP-dependent lipidomic reprogramming as a broad-spectrum antiviral target

Ist Teil von

• Nature communications, 2019-01, Vol.10 (1), p.120-120, Article 120

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Viruses are obligate intracellular microbes that exploit the host metabolic machineries to meet their biosynthetic demands, making these host pathways potential therapeutic targets. Here, by exploring a lipid library, we show that AM580, a retinoid derivative and RAR-α agonist, is highly potent in interrupting the life cycle of diverse viruses including Middle East respiratory syndrome coronavirus and influenza A virus. Using click chemistry, the overexpressed sterol regulatory element binding protein (SREBP) is shown to interact with AM580, which accounts for its broad-spectrum antiviral activity. Mechanistic studies pinpoint multiple SREBP proteolytic processes and SREBP-regulated lipid biosynthesis pathways, including the downstream viral protein palmitoylation and double-membrane vesicles formation, that are indispensable for virus replication. Collectively, our study identifies a basic lipogenic transactivation event with broad relevance to human viral infections and represents SREBP as a potential target for the development of broad-spectrum antiviral strategies.