RT Journal Article
SR Electronic
T1 Unexpected free fatty acid binding pocket in the cryo-EM structure of SARS-CoV-2 spike protein
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.18.158584
DO 10.1101/2020.06.18.158584
A1 Christine Toelzer
A1 Kapil Gupta
A1 Sathish K.N. Yadav
A1 Ufuk Borucu
A1 Frederic Garzoni
A1 Oskar Staufer
A1 Julien Capin
A1 Joachim Spatz
A1 Daniel Fitzgerald
A1 Imre Berger
A1 Christiane Schaffitzel
YR 2020
UL http://biorxiv.org/content/early/2020/06/18/2020.06.18.158584.abstract
AB 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, immune modulation and membrane fluidity. Our structure directly links LA and S, setting the stage for interventions targeting LA binding and metabolic remodeling by SARS-CoV-2.One Sentence Summary A direct structural link between SARS-CoV-2 spike and linoleic acid, a key molecule in inflammation, immune modulation and membrane fluidity.Competing Interest StatementI.B. and D.F. report shareholding in Geneva Biotech SARL unrelated to this Correspondence. I.B and F.G. report shareholding in Imophoron Ltd. unrelated to this Correspondence. A patent application describing drug discovery methods and therapeutic interventions based on the present observations has been filed.