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. Link | PDF | Supporting Information (PDF)
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.
Swedish Long Covid research published in May 2022: https://pubs.acs.org/doi/10.1021/jacs.2c03925 https://svt.se/nyheter/lokalt/ost/forskarnas-upptackt-ett-mojligt-svar-pa-covid-19
