Metabolomics

Dataset Information

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Targeting the SREBP-dependent lipidomic reprogramming by virus infection for broad-spectrum therapeutic intervention


ABSTRACT: Viruses are obligate intracellular parasites that exploit the host metabolic machineries to meet their extraordinary biosynthetic demands. Integrative transcriptomic and lipidomic profiling confirmed that Middle East respiratory syndrome coronavirus (MERS-CoV) infection reprograms the host lipid metabolism. By exploring a bioactive lipid library, we identified a tool compound, AM580 which is highly potent in interrupting the life cycle of diverse viruses including MERS-CoV and influenza A virus.
Using click chemistry, the sterol regulatory element binding protein (SREBP) was identified as the primary cellular target of 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 an ideal target for the development of broad-spectrum intervention strategies.

INSTRUMENT(S): Liquid Chromatography MS - Negative (LC-MS (Negative)), Liquid Chromatography MS - Positive (LC-MS (Positive))

PROVIDER: MTBLS762 | MetaboLights | 2018-11-26

REPOSITORIES: MetaboLights

Dataset's files

Source:
Action DRS
AM580 treated-1-neg.abf Other
AM580 treated-1-pos.abf Other
AM580 treated-2-neg.abf Other
AM580 treated-2-pos.abf Other
AM580 treated-3-neg.abf Other
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Publications


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 p  ...[more]

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