TY - JOUR
T1 - SREBP-dependent lipidomic reprogramming as a broad-spectrum antiviral target
AU - Yuan, Shuofeng
AU - Chu, Hin
AU - Chan, Jasper Fuk Woo
AU - Ye, Zi Wei
AU - Wen, Lei
AU - Yan, Bingpeng
AU - Lai, Pok Man
AU - Tee, Kah Meng
AU - Huang, Jingjing
AU - Chen, Dongdong
AU - Li, Cun
AU - Zhao, Xiaoyu
AU - Yang, Dong
AU - Chiu, Man Chun
AU - Yip, Cyril
AU - Poon, Vincent Kwok Man
AU - Chan, Chris Chung Sing
AU - Sze, Kong Hung
AU - Zhou, Jie
AU - Chan, Ivy Hau Yee
AU - Kok, Kin Hang
AU - To, Kelvin Kai Wang
AU - Kao, Richard Yi Tsun
AU - Lau, Johnson Yiu Nam
AU - Jin, Dong Yan
AU - Perlman, Stanley
AU - Yuen, Kwok Yung
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-018-08015-x
DO - 10.1038/s41467-018-08015-x
M3 - Article
C2 - 30631056
AN - SCOPUS:85059829725
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 120
ER -