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Unexpected free fatty acid binding pocket in the cryo-EM structure of SARS-CoV-2 spike protein

biorxiv. 2020-06; 
Christine Toelzer, Kapil Gupta, Sathish K.N. Yadav, Ufuk Borucu, Frederic Garzoni, Oskar Staufer, Julien Capin, Joachim Spatz, Daniel Fitzgerald, Imre Berger, Christiane Schaffitzel
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COVID-19, caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), represents a global crisis. Key to SARS-CoV-2 therapeutic development is unraveling the mechanisms driving high infectivity, broad tissue tropism and severe pathology. Our cryo-EM structure of SARS-CoV-2 spike (S) glycoprotein reveals that the receptor binding domains (RBDs) tightly and specifically bind the essential free fatty acid (FFA) linoleic acid (LA) in three composite binding pockets. The pocket also appears to be present in the highly pathogenic coronaviruses SARS-CoV and MERS-CoV. Lipid metabolome remodeling is a key feature of coronavirus infection, with LA at its core. LA metabolic pathways are central to inflammation... More