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10.1021/jacs.2c03925

http://scihub22266oqcxt.onion/10.1021/jacs.2c03925
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35579205!9136918!35579205
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suck abstract from ncbi

pmid35579205      J+Am+Chem+Soc 2022 ; 144 (20): 8945-8950
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  • Amyloidogenesis of SARS-CoV-2 Spike Protein #MMPMID35579205
  • Nystrom S; Hammarstrom P
  • J Am Chem Soc 2022[May]; 144 (20): 8945-8950 PMID35579205show ga
  • 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 degrees 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.
  • |*Amyloid/chemistry[MESH]
  • |*COVID-19/complications[MESH]
  • |*Spike Glycoprotein, Coronavirus/chemistry[MESH]
  • |Amino Acid Sequence[MESH]
  • |Amyloidogenic Proteins/chemistry[MESH]
  • |Humans[MESH]
  • |Leukocyte Elastase[MESH]
  • |Peptides/chemistry[MESH]
  • |Post-Acute COVID-19 Syndrome[MESH]
  • |Prospective Studies[MESH]
  • |Protein Structure, Secondary[MESH]


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