Abstract
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 2.85 Å cryo-EM structure of SARS-CoV-2 spike (S) glycoprotein reveals that the receptor binding domains (RBDs) tightly 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. LA binding stabilizes a locked S conformation giving rise to reduced ACE2 interaction in vitro. In human cells, LA supplementation synergizes with the COVID-19 drug remdesivir, suppressing SARS-CoV-2 replication. Our structure directly links LA and S, setting the stage for intervention strategies targeting LA binding by SARS-CoV-2.
Original language | English |
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Article number | eabd3255 |
Number of pages | 12 |
Journal | Science |
Volume | 370 |
Issue number | 6517 |
Early online date | 21 Sept 2020 |
DOIs | |
Publication status | Published - 6 Nov 2020 |
Research Groups and Themes
- Bristol BioDesign Institute
- Covid19
- UNCOVER
- BrisSynBio
- Max Planck Bristol
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Alam, S. R. (Manager), Williams, D. A. G. (Manager), Eccleston, P. E. (Manager) & Greene, D. (Manager)
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Professor Adrian J Mulholland
- Infection and Immunity
- School of Chemistry - Professor
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