期刊
SCIENCE
卷 370, 期 6517, 页码 725-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abd3255
关键词
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资金
- Elizabeth Blackwell Institute for Health Research
- EPSRC [EP/R511663/1, EP/M022609/1]
- University of Bristol
- BrisSynBio, a BBSRC/EPSRC Research Centre for synthetic biology at the University of Bristol [BB/L01386X/1]
- BBSRC [BB/P000940/1, BB/R000484/1]
- Oracle Higher Education and Research program
- EPSRC
- Wellcome Trust [202904/Z/16/Z, 206181/Z/17/Z, 210701/Z/18/Z, 106115/Z/14/Z]
- University of Bristol's Alumni and Friends
- Elisabeth Muerer Foundation
- Max Planck School Matter to Life
- Heidelberg Biosciences International Graduate School
- U.S. Food and Drug Administration [HHSF223201510104C]
- UK Research and Innovation/Medical Research Council (MRC) [MR/V027506/1]
- MRC [MR/V027506/1, MR/R020566/1]
- British Society for Antimicrobial Chemotherapy [BSAC-COVID-30]
- EPSRC Future Vaccine Manufacturing and Research Hub [EP/R013764/1]
- Wellcome Trust [206181/Z/17/Z, 202904/Z/16/Z] Funding Source: Wellcome Trust
- BBSRC [BB/R000484/1, BB/P000940/1, BB/L01386X/1] Funding Source: UKRI
- EPSRC [EP/G007705/1, EP/J010588/1, EP/M022609/1, EP/R029407/1, EP/R013764/1] Funding Source: UKRI
- MRC [MR/R020566/1, MR/V027506/1] Funding Source: UKRI
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.
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