Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein-Reference-Cited by-同舟云学术

Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein

Published:2020-11-06 Issue:6517 Volume:370 Page:725-730
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Toelzer Christine¹²^ORCID,Gupta Kapil¹²^ORCID,Yadav Sathish K. N.¹²^ORCID,Borucu Ufuk¹²^ORCID,Davidson Andrew D.³^ORCID,Kavanagh Williamson Maia³^ORCID,Shoemark Deborah K.¹²^ORCID,Garzoni Frederic⁴^ORCID,Staufer Oskar⁵⁶⁷⁸^ORCID,Milligan Rachel³^ORCID,Capin Julien¹²^ORCID,Mulholland Adrian J.⁹^ORCID,Spatz Joachim⁵⁶⁷⁸,Fitzgerald Daniel¹⁰,Berger Imre¹²⁸⁹^ORCID,Schaffitzel Christiane¹²^ORCID

Affiliation:

1. School of Biochemistry, University of Bristol, 1 Tankard’s Close, Bristol BS8 1TD, UK.

2. Bristol Synthetic Biology Centre BrisSynBio, 24 Tyndall Ave., Bristol BS8 1TQ, UK.

3. School of Cellular and Molecular Medicine, University of Bristol, University Walk, Bristol BS8 1TD, UK.

4. Imophoron Ltd., St. Philips Central, Albert Rd., St. Philips, Bristol BS2 0XJ, UK.

5. Department for Cellular Biophysics, Max Planck Institute for Medical Research, Jahnstraße 29, 69120 Heidelberg, Germany.

6. Institute for Physical Chemistry, Department for Biophysical Chemistry, University of Heidelberg, Im Neuenheimer Feld 253, 69120 Heidelberg, Germany.

7. Max Planck School Matter to Life, Jahnstraße 29, D-69120 Heidelberg, Germany.

8. Max Planck Bristol Centre for Minimal Biology, Cantock’s Close, Bristol BS8 1TS, UK.

9. School of Chemistry, University of Bristol, Cantock’s Close, Bristol BS8 1TS, UK.

10. Geneva Biotech Sàrl, Avenue de la Roseraie 64, 1205, Geneva, Switzerland.

Abstract

Locking down the SARS-CoV-2 spike Many efforts to develop therapies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are focused on the spike (S) protein trimer that binds to the host receptor. Structures of trimeric S protein show its receptor-binding domain in either an up or a down conformation. Toelzer et al. produced SARS-CoV-2 S in insect cells and determined the structure by cryo–electron microscopy. In their dataset, the closed form was predominant and was stabilized by binding linoleic acid, an essential fatty acid. A similar binding pocket appears to be present in previous highly pathogenic coronaviruses, and past studies suggested links between viral infection and fatty acid metabolism. The pocket could be exploited to develop inhibitors that trap S protein in the closed conformation. Science , this issue p. 725

Funder

Oracle

Wellcome

Medical Research Council

Engineering and Physical Sciences Research Council

British Society for Antimicrobial Chemotherapy

United States Food and Drug Administration

UK Research and Innovation / Medical Research Council

Max Planck Society

Biotechnology and Biological Sciences Research Council

Elisabeth Muerer Foundation

Publisher