Amyloidogenesis of SARS-CoV-2 Spike Protein, 2022, Nyström & Hammarström

Discussion in 'Long Covid research' started by SNT Gatchaman, May 18, 2022.

  1. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    Amyloidogenesis of SARS-CoV-2 Spike Protein
    Sofie Nyström, Per Hammarström

    Abstract
    SARS-CoV-2 infection is associated with a surprising number of morbidities. Uncanny similarities with amyloid-disease associated blood coagulation and fibrinolytic disturbances together with neurologic and cardiac problems led us to investigate the amyloidogenicity of the SARS-CoV-2 spike protein (S-protein).

    Amyloid fibril assays of peptide library mixtures and theoretical predictions identified seven amyloidogenic sequences within the S-protein. All seven peptides in isolation formed aggregates during incubation at 37 °C. Three 20-amino acid long synthetic spike peptides (sequence 192-211, 601-620, 1166-1185) fulfilled three amyloid fibril criteria: nucleation dependent polymerization kinetics by ThT, Congo red positivity, and ultrastructural fibrillar morphology.

    Full-length folded S-protein did not form amyloid fibrils, but amyloid-like fibrils with evident branching were formed during 24 h of S-protein coincubation with the protease neutrophil elastase (NE) in vitro. NE efficiently cleaved S-protein, rendering exposure of amyloidogenic segments and accumulation of the amyloidogenic peptide 194-203, part of the most amyloidogenic synthetic spike peptide.

    NE is overexpressed at inflamed sites of viral infection. Our data propose a molecular mechanism for potential amyloidogenesis of SARS-CoV-2 S-protein in humans facilitated by endoproteolysis. The prospective of S-protein amyloidogenesis in COVID-19 disease associated pathogenesis can be important in understanding the disease and long COVID-19.

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    Last edited: May 18, 2022
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  2. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    SNT Gatchaman Senior Member (Voting Rights)

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    SNT Gatchaman Senior Member (Voting Rights)

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    SNT Gatchaman Senior Member (Voting Rights)

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    SNT Gatchaman Senior Member (Voting Rights)

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  7. SNT Gatchaman

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    Screen Shot 2022-05-19 at 9.46.09 AM Large.jpeg
     
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  8. SNT Gatchaman

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  9. Kalliope

    Kalliope Senior Member (Voting Rights)

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    Linköping University has a good article about the study:
    Possible discovery of mechanism behind mysterious COVID-19 symptoms

    quote:
    In patients with serious and long-term COVID-19, disturbed blood coagulation has often been observed. Now, researchers at LiU have discovered that the body’s immune system can affect the spike protein on the surface of the SARS-CoV-2 virus, leading to the production of a misfolded spike protein called amyloid. The discovery points to a possible connection between harmful amyloid production and symptoms of COVID-19.
     
  10. Lindberg

    Lindberg Established Member (Voting Rights)

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