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-Structure paper
タイトル | The free fatty acid-binding pocket is a conserved hallmark in pathogenic β-coronavirus spike proteins from SARS-CoV to Omicron. |
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ジャーナル・号・ページ | Sci Adv, Vol. 8, Issue 47, Page eadc9179, Year 2022 |
掲載日 | 2022年11月25日 |
![]() | Christine Toelzer / Kapil Gupta / Sathish K N Yadav / Lorna Hodgson / Maia Kavanagh Williamson / Dora Buzas / Ufuk Borucu / Kyle Powers / Richard Stenner / Kate Vasileiou / Frederic Garzoni / Daniel Fitzgerald / Christine Payré / Gunjan Gautam / Gérard Lambeau / Andrew D Davidson / Paul Verkade / Martin Frank / Imre Berger / Christiane Schaffitzel / ![]() ![]() ![]() |
PubMed 要旨 | 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 ...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. |
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手法 | EM (単粒子) |
解像度 | 2.48 - 3.3 Å |
構造データ | EMDB-14717, PDB-7zh1: EMDB-14718, PDB-7zh2: EMDB-14724, PDB-7zh5: |
化合物 | ![]() ChemComp-EIC: ![]() ChemComp-NAG: |
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