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Strikingly Different Roles of SARS-CoV-2 Fusion Peptides Uncovered by Neutron Scattering.

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cam.depositDate2022-01-07
cam.issuedOnline2022-02-14
cam.orpheus.counter2
cam.orpheus.successWed Mar 23 10:26:22 GMT 2022 - Embargo updated*
datacite.ispreviousversionof.handlehttps://www.repository.cam.ac.uk/handle/1810/335206
dc.contributor.authorSantamaria, Andreas
dc.contributor.authorBatchu, Krishna C
dc.contributor.authorMatsarskaia, Olga
dc.contributor.authorPrévost, Sylvain F
dc.contributor.authorRusso, Daniela
dc.contributor.authorNatali, Francesca
dc.contributor.authorSeydel, Tilo
dc.contributor.authorHoffmann, Ingo
dc.contributor.authorLaux, Valérie
dc.contributor.authorHaertlein, Michael
dc.contributor.authorDarwish, Tamim A
dc.contributor.authorRussell, Robert A
dc.contributor.authorCorucci, Giacomo
dc.contributor.authorFragneto, Giovanna
dc.contributor.authorMaestro, Armando
dc.contributor.authorZaccai, Nathan
dc.contributor.orcidSantamaria, Andreas [0000-0002-6151-4406]
dc.contributor.orcidMatsarskaia, Olga [0000-0002-7293-7287]
dc.contributor.orcidSeydel, Tilo [0000-0001-9630-1630]
dc.contributor.orcidHoffmann, Ingo [0000-0001-7178-6467]
dc.contributor.orcidDarwish, Tamim A [0000-0001-7704-1837]
dc.contributor.orcidMaestro, Armando [0000-0002-7791-8130]
dc.contributor.orcidZaccai, Nathan [0000-0002-1476-2044]
dc.date.accessioned2022-01-11T00:30:40Z
dc.date.available2022-01-11T00:30:40Z
dc.date.issued2022-02-23
dc.date.updated2022-01-07T14:10:17Z
dc.description.abstractCoronavirus 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.
dc.identifier.doi10.17863/CAM.80033
dc.identifier.eissn1520-5126
dc.identifier.issn0002-7863
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332586
dc.language.isoeng
dc.publisherAmerican Chemical Society (ACS)
dc.publisher.departmentC.I.M.R. Clinical Biochemistry
dc.rightsAll Rights Reserved
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserved
dc.titleStrikingly Different Roles of SARS-CoV-2 Fusion Peptides Uncovered by Neutron Scattering.
dc.typeArticle
dcterms.dateAccepted2021-12-24
prism.publicationNameJ Am Chem Soc
pubs.funder-project-idWellcome Trust (090909/Z/09/Z)
pubs.funder-project-idWellcome Trust (207455/Z/17/Z)
pubs.licence-display-nameApollo Repository Deposit Licence Agreement
pubs.licence-identifierapollo-deposit-licence-2-1
rioxxterms.typeJournal Article/Review
rioxxterms.versionAM
rioxxterms.versionofrecord10.1021/jacs.1c09856

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