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

The study titled “SARS-CoV-2 Spike amyloid fibrils specifically and selectively accelerates amyloid fibril formation of human prion protein and the amyloid β peptide” provides groundbreaking insights into the potential link between COVID-19 and neurodegenerative diseases (NDs).

Here’s a detailed summary:

Background and Objectives:

  • The study investigates the association between COVID-19 infection and the initiation or acceleration of NDs, including Alzheimer’s disease (AD) and Creutzfeldt-Jakob disease (CJD). It focuses on the conversion of human proteins into misfolded amyloid fibrils, a common feature in these diseases.
  • The researchers previously described a mechanism for amyloid fibril formation of the SARS-CoV-2 spike protein. This study aims to explore whether these spike protein-derived amyloids can accelerate amyloid formation in other proteins associated with NDs​​.

Methodology:

  • The study used an in vitro assay to test the cross-seeding effect of amyloid fibrils derived from the SARS-CoV-2 spike protein on human prion protein (HuPrP) and Aβ1-42 peptide, which are associated with CJD and AD, respectively.
  • Seven different 20-amino acid long peptides from the SARS-CoV-2 spike protein were used to form amyloid fibrils, known as Spike-seeds, and their effect on the formation of HuPrP and Aβ1-42 fibrils was examined​​.

Key Findings:

  • The addition of these spike-derived fibrils significantly increased the rate of fibril formation for both HuPrP and Aβ1-42. Notably, Spike532 was the most efficient in seeding HuPrP, while Spike601 was most effective in seeding Aβ1-42.
  • This acceleration was not observed with control amyloid fibrils from other proteins, suggesting that the effect is specific to spike-derived amyloids.
  • The study highlights the substrate-dependent selectivity of the cross-seeding activity by these spike amyloid fibrils​​.

Discussion and Implications:

  • The findings suggest that viral amyloids, like those derived from the SARS-CoV-2 spike protein, may have unique properties that make them more prone to induce misfolding in human proteins, potentially contributing to the development of NDs.
  • This research aligns with the idea that there is a lack of evolutionary co-adaptation between human and viral proteomes, making humans more susceptible to cross-seeding from viral amyloids.
  • The study advocates for intensified research into virus amyloids as potential triggers for protein misfolding and amyloid formation in NDs, particularly in light of reports linking CJD manifestations temporally close to SARS-CoV-2 infection or vaccination​​.

In conclusion, this study sheds new light on the potential role of SARS-CoV-2 spike protein in accelerating amyloid formation related to neurodegenerative diseases, offering a novel avenue for understanding and potentially intervening in the progression of these conditions.

Read More: https://www.biorxiv.org/content/10.1101/2023.09.01.555834v1.abstract

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