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http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/7467| Amyloidogenesis of SARS-CoV-2 Spike Protein | |
| Sofie Nyström Per Hammarstrom | |
| Acceso Abierto | |
| Atribución-NoComercial-SinDerivadas | |
| https://doi.org/10.1101/2021.12.16.472920 | |
| https://www.biorxiv.org/content/10.1101/2021.12.16.472920v1 | |
| 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 191-210, 599-618, 1165-1184) 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 hours of S-protein co-incubation with the protease neutrophil elastase (NE) in vitro. NE efficiently cleaved S-protein rendering exposure of amyloidogenic segments and accumulation of the peptide 193-202, part of the most amyloidogenic synthetic Spike peptide. NE is overexpressed at inflamed sites of viral infection and at vaccine injection sites. Our data propose a molecular mechanism for amyloidogenesis of SARS-CoV-2 S-protein in humans facilitated by endoproteolysis. The potential implications of S-protein amyloidogenesis in COVID-19 disease associated pathogenesis and consequences following S-protein based vaccines should be addressed in understanding the disease, long COVID-19, and vaccine side effects. | |
| medRxiv and bioRxiv | |
| 16-12-2021 | |
| Preimpreso | |
| www.biorxiv.org | |
| Inglés | |
| Epidemia COVID-19 | |
| Investigadores Público en general | |
| VIRUS RESPIRATORIOS | |
| Versión publicada | |
| publishedVersion - Versión publicada | |
| Aparece en las colecciones: | Artículos científicos |
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| Amyloidogenesis of SARS COV 2 Spike Protein.pdf | 2.31 MB | Adobe PDF | Visualizar/Abrir |