The free fatty acid–binding pocket is a conserved hallmark in pathogenic β-coronavirus spike proteins from SARS-CoV to Omicron

Archive ouverte

Toelzer, Christine | Gupta, Kapil | Yadav, Sathish | Hodgson, Lorna | Williamson, Maia Kavanagh | Buzas, Dora | Borucu, Ufuk | Powers, Kyle | Stenner, Richard | Vasileiou, Kate | Garzoni, Frederic | Fitzgerald, Daniel | Payré, Christine | Gautam, Gunjan | Lambeau, Gérard | Davidson, Andrew | Verkade, Paul | Frank, Martin | Berger, Imre | Schaffitzel, Christiane

Edité par CCSD ; American Association for the Advancement of Science (AAAS) -

International audience. As coronavirus disease 2019 (COVID-19) persists, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) emerge, accumulating spike (S) glycoprotein mutations. S receptor binding domain (RBD) comprises a free fatty acid (FFA)–binding pocket. FFA binding stabilizes a locked S conformation, interfering with virus infectivity. We provide evidence that the pocket is conserved in pathogenic β-coronaviruses (β-CoVs) infecting humans. SARS-CoV, MERS-CoV, SARS-CoV-2, and VOCs bind the essential FFA linoleic acid (LA), while binding is abolished by one mutation in common cold–causing HCoV-HKU1. In the SARS-CoV S structure, LA stabilizes the locked conformation, while the open, infectious conformation is devoid of LA. Electron tomography of SARS-CoV-2–infected cells reveals that LA treatment inhibits viral replication, resulting in fewer deformed virions. Our results establish FFA binding as a hallmark of pathogenic β-CoV infection and replication, setting the stage for FFA-based antiviral strategies to overcome COVID-19.

• Description
• Sujet/Public
• Outil
• Outil d'anticipation
• Mémoire et thèse
• Gestion