Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein
Coronavirus disease 2019 (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 that drive high infectivity, broad tissue tropism, and severe pathology. Our 2.85-angstrom cryo–electron microscopy structure of SARS-CoV-2 spike (S) glycoprotein reveals that the receptor binding domains tightly bind the essential free fatty acid linoleic acid (LA) in three composite binding pockets. A similar pocket also appears to be present in the highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). LA binding stabilizes a locked S conformation, resulting in reduced angiotensin-converting enzyme 2 (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 that target LA binding by SARS-CoV-2.
Source: ScienceNOW - Category: Science Authors: Toelzer, C., Gupta, K., Yadav, S. K. N., Borucu, U., Davidson, A. D., Kavanagh Williamson, M., Shoemark, D. K., Garzoni, F., Staufer, O., Milligan, R., Capin, J., Mulholland, A. J., Spatz, J., Fitzgerald, D., Berger, I., Schaffitzel, C. Tags: Biochemistry reports Source Type: news
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