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TitleA neutralizing epitope on the SD1 domain of SARS-CoV-2 spike targeted following infection and vaccination.
Journal, issue, pagesCell Rep, Vol. 40, Issue 8, Page 111276, Year 2022
Publish dateAug 23, 2022
AuthorsJeffrey Seow / Hataf Khan / Annachiara Rosa / Valeria Calvaresi / Carl Graham / Suzanne Pickering / Valerie E Pye / Nora B Cronin / Isabella Huettner / Michael H Malim / Argyris Politis / Peter Cherepanov / Katie J Doores /
PubMed AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike is the target for neutralizing antibodies elicited following both infection and vaccination. While extensive research has shown that ...Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike is the target for neutralizing antibodies elicited following both infection and vaccination. While extensive research has shown that the receptor binding domain (RBD) and, to a lesser extent, the N-terminal domain (NTD) are the predominant targets for neutralizing antibodies, identification of neutralizing epitopes beyond these regions is important for informing vaccine development and understanding antibody-mediated immune escape. Here, we identify a class of broadly neutralizing antibodies that bind an epitope on the spike subdomain 1 (SD1) and that have arisen from infection or vaccination. Using cryo-electron microscopy (cryo-EM) and hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS), we show that SD1-specific antibody P008_60 binds an epitope that is not accessible within the canonical prefusion states of the SARS-CoV-2 spike, suggesting a transient conformation of the viral glycoprotein that is vulnerable to neutralization.
External linksCell Rep / PubMed:35981534 / PubMed Central
MethodsEM (single particle)
Resolution4.31 Å
Structure data

14591

7zbu

EMDB-14591, PDB-7zbu:
CryoEM structure of SARS-CoV-2 spike monomer in complex with neutralising antibody P008_60
Method: EM (single particle) / Resolution: 4.31 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-3Q9:
3-[5-[(4-ethyl-3-methyl-5-oxidanylidene-pyrrol-2-yl)methyl]-2-[[5-[(3-ethyl-4-methyl-5-oxidanylidene-pyrrol-2-yl)methyl]-3-(3-hydroxy-3-oxopropyl)-4-methyl-1H-pyrrol-2-yl]methyl]-4-methyl-1H-pyrrol-3-yl]propanoic acid

Source
  • homo sapiens (human)
  • severe acute respiratory syndrome coronavirus 2
KeywordsVIRAL PROTEIN / covid-19 / SARS-CoV-2 / spike / neutralizing antibody / immunity

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