Reduction of hemagglutination induced by a SARS-CoV-2 spike protein fragment using an amyloid-binding benzothiazole amphiphile, 2024, Li et al.

[SNT Gatchaman]

Reduction of hemagglutination induced by a SARS-CoV-2 spike protein fragment using an amyloid-binding benzothiazole amphiphile
Li, Meihan; Castro Lingl, Sascha; Yang, Jerry

COVID-19 infection is associated with a variety of vascular occlusive morbidities. However, a comprehensive understanding of how this virus can induce vascular complications remains lacking.

Here, we show that a peptide fragment of SARS-CoV-2 spike protein, S192 (sequence 192-211), is capable of forming amyloid-like aggregates that can induce agglutination of red blood cells, which was not observed with low- and non-aggregated S192 peptide. We subsequently screened eight amyloid-binding molecules and identified BAM1-EG6, a benzothiazole amphiphile, as a promising candidate capable of binding to aggregated S192 and partially inhibiting its agglutination activity.

These results provide new insight into a potential molecular mechanism for the capability of spike protein metabolites to contribute to COVID-19-related blood complications and suggest a new therapeutic approach for combating microvascular morbidities in COVID-19 patients.

Link | PDF (Nature Scientific Reports) [Open Access]

 

[SNT Gatchaman]

Recently, several 20-amino acid long segments within the SARS-CoV-2 spike protein were generated and reported to exhibit amyloidogenic properties. Among them, S192 peptide, with the amino acid sequence 192-211 FVFKNIDGYFKIYSKHTPIN, was identified as the most amyloidogenic segment, fulfilling all three characteristics common to all amyloids. Notably, this group found that full-length spike protein did not form amyloids on its own under similar conditions as the peptide segments. However, when the spike protein was incubated with neutrophil elastase (NE), a serine protease involved in immune responses, for a duration of 24 h in vitro, the formation of amyloid-like fibrils was observed.

Overall, the present study provides evidence that the amyloidogenic peptide derived from the SARS-CoV-2 spike protein, S192, can induce the agglutination of red blood cells, which could potentially contribute to the microvascular morbidities observed in COVID-19 patients.

It is noteworthy that S192 lacks any known glycosylation sites, and only the aggregated form of S192 is capable of inducing hemagglutination. This result suggests a novel mechanism for agglutination activity for this spike protein metabolite that operates independently of the interaction of the glycosylation sites with cell surface sialoglycoproteins. Furthermore, this study identifies an amyloidbinding molecule, BAM1-EG6 , that can partially intervene in spike peptide-induced hemagglutination, which serves as proof-of-concept for a potential therapeutic strategy that involves amyloid-binding agents to attenuate vascular occlusive complications caused by the presence of metabolic products of the SARS-CoV-2 spike protein.