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Strikingly Different Roles of SARS-CoV-2 Fusion Peptides Uncovered by Neutron Scattering.
Santamaria, Andreas; Batchu, Krishna C; Matsarskaia, Olga; Prévost, Sylvain F; Russo, Daniela; Natali, Francesca; Seydel, Tilo; Hoffmann, Ingo; Laux, Valérie; Haertlein, Michael; Darwish, Tamim A; Russell, Robert A; Corucci, Giacomo; Fragneto, Giovanna; Maestro, Armando; Zaccai, Nathan R.
  • Santamaria A; Institut Laue-Langevin, 38042 Grenoble, France.
  • Batchu KC; Departamento de Química Física, Universidad Complutense de Madrid, 28040 Madrid, Spain.
  • Matsarskaia O; Institut Laue-Langevin, 38042 Grenoble, France.
  • Prévost SF; Institut Laue-Langevin, 38042 Grenoble, France.
  • Russo D; Institut Laue-Langevin, 38042 Grenoble, France.
  • Natali F; Institut Laue-Langevin, 38042 Grenoble, France.
  • Seydel T; CNR-IOM & INSIDE@ILL, 38042 Grenoble, France.
  • Hoffmann I; Institut Laue-Langevin, 38042 Grenoble, France.
  • Laux V; CNR-IOM & INSIDE@ILL, 38042 Grenoble, France.
  • Haertlein M; Institut Laue-Langevin, 38042 Grenoble, France.
  • Darwish TA; Institut Laue-Langevin, 38042 Grenoble, France.
  • Russell RA; Institut Laue-Langevin, 38042 Grenoble, France.
  • Corucci G; Institut Laue-Langevin, 38042 Grenoble, France.
  • Fragneto G; National Deuteration Facility, ANSTO-Sidney, Lucas Heights, NSW 2234, Australia.
  • Maestro A; National Deuteration Facility, ANSTO-Sidney, Lucas Heights, NSW 2234, Australia.
  • Zaccai NR; Institut Laue-Langevin, 38042 Grenoble, France.
J Am Chem Soc ; 144(7): 2968-2979, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1683928
ABSTRACT
Coronavirus disease-2019 (COVID-19), a potentially lethal respiratory illness caused by the coronavirus SARS-CoV-2, emerged in the end of 2019 and has since spread aggressively across the globe. A thorough understanding of the molecular mechanisms of cellular infection by coronaviruses is therefore of utmost importance. A critical stage in infection is the fusion between viral and host membranes. Here, we present a detailed investigation of the role of selected SARS-CoV-2 Spike fusion peptides, and the influence of calcium and cholesterol, in this fusion process. Structural information from specular neutron reflectometry and small angle neutron scattering, complemented by dynamics information from quasi-elastic and spin-echo neutron spectroscopy, revealed strikingly different functions encoded in the Spike fusion domain. Calcium drives the N-terminal of the Spike fusion domain to fully cross the host plasma membrane. Removing calcium, however, reorients the peptide back to the lipid leaflet closest to the virus, leading to significant changes in lipid fluidity and rigidity. In conjunction with other regions of the fusion domain, which are also positioned to bridge and dehydrate viral and host membranes, the molecular events leading to cell entry by SARS-CoV-2 are proposed.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Peptide Fragments / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / Lipid Bilayers Type of study: Randomized controlled trials Language: English Journal: J Am Chem Soc Year: 2022 Document Type: Article Affiliation country: Jacs.1c09856

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Peptide Fragments / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / Lipid Bilayers Type of study: Randomized controlled trials Language: English Journal: J Am Chem Soc Year: 2022 Document Type: Article Affiliation country: Jacs.1c09856