S-acylation controls SARS-CoV-2 membrane lipid organization and enhances infectivity.
Dev Cell
; 56(20): 2790-2807.e8, 2021 10 25.
Article
in English
| MEDLINE | ID: covidwho-1446559
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Acylation
/
SARS-CoV-2
/
COVID-19 Drug Treatment
/
Membrane Lipids
Limits:
Humans
Language:
English
Journal:
Dev Cell
Journal subject:
Embryology
Year:
2021
Document Type:
Article
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