SREBP-dependent lipidomic reprogramming as a broad-spectrum antiviral target.
Nat Commun
; 10(1): 120, 2019 01 10.
Article
em En
| MEDLINE
| ID: mdl-30631056
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tetra-Hidronaftalenos
/
Replicação Viral
/
Benzoatos
/
Proteínas de Ligação a Elemento Regulador de Esterol
/
Metabolismo dos Lipídeos
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article