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S-acylation controls SARS-CoV-2 membrane lipid organization and enhances infectivity
Developmental Cell  (IF12.27),  Pub Date : 2021-10-01, DOI: 10.1016/j.devcel.2021.09.016
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

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.