Preprint SARS-CoV-2 Spike amyloid fibrils specifically and selectively accelerates amyloid fibril formation of human prion protein and the amyloid β peptide,

[EndME]

SARS-CoV-2 Spike amyloid fibrils specifically and selectively accelerates amyloid fibril formation of human prion protein and the amyloid β peptide

Abstract
An increasing number of reports suggest an association between COVID-19 infection and initiation or acceleration of neurodegenerative diseases including Alzheimer's disease (AD) and Creutzfeldt-Jakob disease (CJD). Both these diseases and several other neurodegenerative diseases are caused by conversion of human proteins into a misfolded, aggregated amyloid fibril state. The fibril formation process is self-perpetuating by seeded conversion from preformed fibril seeds.

We recently described a plausible mechanism for amyloid fibril formation of SARS-CoV-2 spike protein. Spike-protein formed amyloid fibrils upon cleavage by neutrophil elastase, abundant in the inflammatory response to COVID-19 infection. We here provide evidence of significant Spike-amyloid fibril seeded acceleration of amyloid formation of CJD associated human prion protein (HuPrP) using an in vitro conversion assay. By seeding the HuPrP conversion assay with other in vitro generated disease associated amyloid fibrils we demonstrate that this is not a general effect but a specific feature of spike-amyloid fibrils.

We also showed that the amyloid fibril formation of AD associated Aβ1-42 was accelerated by Spike-amyloid fibril seeds. Of seven different 20-amino acid long peptides, Spike532 (532NLVKNKCVNFNFNGLTGTGV551) was most efficient in seeding HuPrP and Spike601 (601GTNTSNQVAVLYQDVNCTEV620) was most effective in seeding Aβ1-42, suggesting substrate dependent selectivity of the cross-seeding activity.

Albeit purely in vitro, our data suggest that cross-seeding by Spike-amyloid fibrils can be implicated in the increasing number of reports of CJD, AD, and possibly other neurodegenerative diseases in the wake of COVID-19.


https://www.biorxiv.org/content/10.1101/2023.09.01.555834v1

 

[SNT Gatchaman]

AD is linked to formation of extracellular amyloid plaques with the Aβ peptide [...] and intracellular neurofibrillary tangles composed of Tau protein. Prion diseases are caused by the misfolding and aggregation of the prion protein, PrP, that is abundant on the extracellular surface of all neuronal cells [...] more evidence is pointing towards the possibility of cross-seeding, that is that amyloids formed of one type of protein can induce amyloid formation of another protein

SARS-CoV-2 Spike proteins forms amyloid when cleaved by neutrophil elastase [...] abundant in covid induced inflammation

Amyloid derived from S CoV-2 spike protein has the potential to hamper fibrinolysis of seeded fibrin and hence might be one explanation for microclot formation in severe and long COVID-19

That reference to their previous work is in thread Amyloidogenesis of SARS-CoV-2 Spike Protein (2022)

Spike protein produced in the host as response to mRNA vaccine, as deduced by specific amino acid substitutions, persists in blood samples from 50% of vaccinated individuals for between 67 and 187 days after mRNA vaccination. Such prolonged Spike protein exposure has previously been hypothesized to stem from residual virus reservoirs, but evidently this can occur also as consequence of mRNA vaccination.

That's a very up-to-date reference (2 days ago): Detection of recombinant Spike protein in the blood of individuals vaccinated against SARS-CoV-2: Possible molecular mechanisms (2023, PROTEOMICS – Clinical Applications)

 

[SNT Gatchaman]

During the past 3 years, several case reports of Creutzfeldt-Jakob disease (CJD) manifestation in parallel with COVID-19 infection or vaccination have been published.

Aβ aggregates were found postmortem in brains of young COVID-19 infected patients. COVID-19 imposed 1.69 increased risk for new diagnosis of AD within 360 days at age >65 years.

The reaction where a protein is insulted by a small amount of preformed amyloid fibrils of the same protein sequence is known as homologous seeding or self-seeding. [...] well established and the literature is vast.

If the added amyloid fibrils instead are composed of a different fibril this is called heterologous seeding or cross-seeding. [...] Cross-seeding is rarely as efficient as self-seeding.

We here demonstrate that both the AD associated peptide Aβ1-42 and the CJD associated human prion protein are susceptible to cross-seeding from amyloids derived from the SARSCoV-2 Spike protein.

the lack of co-evolution between the human and the viral proteomes, have left humans less protected from cross-seeding from viral amyloids than from self-generated amyloids.

Putting this together with the rigorous exploration [...] regarding lingering increased risk of [Neurodegenerative Diseases] decades after viral infection advocates for an intensified research activity on the concept of virus amyloid as a potential triggering factor for protein misfolding and amyloid formation in NDs. Several recent reports of CJD manifesting temporally close to SARS-CoV-2 infection or vaccination with SARS-CoV-2 Spike protein derivatives also highlights the need to investigate possible links.

 

[Ash]

SARS-CoV-2 Spike amyloid fibrils specifically and selectively accelerates amyloid fibril formation of human prion protein and the amyloid β peptide

Abstract
An increasing number of reports suggest an association between COVID-19 infection and initiation or acceleration of neurodegenerative diseases including Alzheimer's disease (AD) and Creutzfeldt-Jakob disease (CJD). Both these diseases and several other neurodegenerative diseases are caused by conversion of human proteins into a misfolded, aggregated amyloid fibril state. The fibril formation process is self-perpetuating by seeded conversion from preformed fibril seeds.

We recently described a plausible mechanism for amyloid fibril formation of SARS-CoV-2 spike protein. Spike-protein formed amyloid fibrils upon cleavage by neutrophil elastase, abundant in the inflammatory response to COVID-19 infection. We here provide evidence of significant Spike-amyloid fibril seeded acceleration of amyloid formation of CJD associated human prion protein (HuPrP) using an in vitro conversion assay. By seeding the HuPrP conversion assay with other in vitro generated disease associated amyloid fibrils we demonstrate that this is not a general effect but a specific feature of spike-amyloid fibrils.

We also showed that the amyloid fibril formation of AD associated Aβ1-42 was accelerated by Spike-amyloid fibril seeds. Of seven different 20-amino acid long peptides, Spike532 (532NLVKNKCVNFNFNGLTGTGV551) was most efficient in seeding HuPrP and Spike601 (601GTNTSNQVAVLYQDVNCTEV620) was most effective in seeding Aβ1-42, suggesting substrate dependent selectivity of the cross-seeding activity.

Albeit purely in vitro, our data suggest that cross-seeding by Spike-amyloid fibrils can be implicated in the increasing number of reports of CJD, AD, and possibly other neurodegenerative diseases in the wake of COVID-19.


https://www.biorxiv.org/content/10.1101/2023.09.01.555834v1

More incredibly upsetting and completely unsurprising news.