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  Synthetic virions reveal fatty acid-coupled adaptive immunogenicity of SARS-CoV-2 spike glycoprotein

Staufer, O., Gupta, K., Hernandez Bücher, J. E., Kohler, F., Sigl, C., Singh, G., et al. (2022). Synthetic virions reveal fatty acid-coupled adaptive immunogenicity of SARS-CoV-2 spike glycoprotein. Nature Communications, 13: 868, pp. 1-13. doi:10.1038/s41467-022-28446-x.

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Staufer, Oskar1, Author              
Gupta, Kapil, Author
Hernandez Bücher, Jochen Estebano1, Author              
Kohler, Fabian, Author
Sigl, Christian, Author
Singh, Gunjita, Author
Vasileiou, Kate, Author
Relimpio, Ana Yagüe1, Author              
Macher, Meline1, Author              
Fabritz, Sebastian2, Author              
Dietz, Hendrik3, Author              
Cavalcanti Adam, Elisabetta Ada1, Author              
Schaffitzel, Christiane, Author
Ruggieri, Alessia, Author
Platzman, Ilia1, Author              
Berger, Imre, Author
Spatz, Joachim P.1, Author              
Affiliations:
1Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society, ou_2364731              
2Chemical Biology, Max Planck Institute for Medical Research, Max Planck Society, ou_2364732              
3Max Planck Institute for Medical Research, Max Planck Society, ou_1125545              

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 Abstract: SARS-CoV-2 infection is a major global public health concern with incompletely understood pathogenesis. The SARS-CoV-2 spike (S) glycoprotein comprises a highly conserved free fatty acid binding pocket (FABP) with unknown function and evolutionary selection advantage1,2. Deciphering FABP impact on COVID-19 progression is challenged by the heterogenous nature and large molecular variability of live virus. Here we create synthetic minimal virions (MiniVs) of wild-type and mutant SARS-CoV-2 with precise molecular composition and programmable complexity by bottom-up assembly. MiniV-based systematic assessment of S free fatty acid (FFA) binding reveals that FABP functions as an allosteric regulatory site enabling adaptation of SARS-CoV-2 immunogenicity to inflammation states via binding of pro-inflammatory FFAs. This is achieved by regulation of the S open-to-close equilibrium and the exposure of both, the receptor binding domain (RBD) and the SARS-CoV-2 RGD motif that is responsible for integrin co-receptor engagement. We find that the FDA-approved drugs vitamin K and dexamethasone modulate S-based cell binding in an FABP-like manner. In inflammatory FFA environments, neutralizing immunoglobulins from human convalescent COVID-19 donors lose neutralization activity. Empowered by our MiniV technology, we suggest a conserved mechanism by which SARS-CoV-2 dynamically couples its immunogenicity to the host immune response.

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Language(s): eng - English
 Dates: 2021-07-092022-01-242022-02-14
 Publication Status: Published online
 Pages: 13
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 Table of Contents: -
 Rev. Type: Peer
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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 13 Sequence Number: 868 Start / End Page: 1 - 13 Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723