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  • S-acylation controls SARS-CoV-2 membrane lipid organization and enhances infectivity.

S-acylation controls SARS-CoV-2 membrane lipid organization and enhances infectivity.

Developmental cell (2021-10-03)
Francisco S Mesquita, Laurence Abrami, Oksana Sergeeva, Priscilla Turelli, Enya Qing, Béatrice Kunz, Charlène Raclot, Jonathan Paz Montoya, Luciano A Abriata, Tom Gallagher, Matteo Dal Peraro, Didier Trono, Giovanni D'Angelo, F Gisou van der Goot
ABSTRACT

SARS-CoV-2 virions are surrounded by a lipid bilayer that contains membrane proteins such as spike, responsible for target-cell binding and virus fusion. We found that during SARS-CoV-2 infection, spike becomes lipid modified, through the sequential action of the S-acyltransferases ZDHHC20 and 9. Particularly striking is the rapid acylation of spike on 10 cytosolic cysteines within the ER and Golgi. Using a combination of computational, lipidomics, and biochemical approaches, we show that this massive lipidation controls spike biogenesis and degradation, and drives the formation of localized ordered cholesterol and sphingolipid-rich lipid nanodomains in the early Golgi, where viral budding occurs. Finally, S-acylation of spike allows the formation of viruses with enhanced fusion capacity. Our study points toward S-acylating enzymes and lipid biosynthesis enzymes as novel therapeutic anti-viral targets.

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