Reduction of hemagglutination induced by a SARS-CoV-2 spike protein fragment using an amyloid-binding benzothiazole amphiphile

Sci Rep. 2024 May 29;14(1):12317. doi: 10.1038/s41598-024-59585-4.

Abstract

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.

MeSH terms

  • Amyloid / metabolism
  • Benzothiazoles* / chemistry
  • Benzothiazoles* / pharmacology
  • COVID-19* / metabolism
  • COVID-19* / virology
  • Erythrocytes / drug effects
  • Erythrocytes / metabolism
  • Erythrocytes / virology
  • Hemagglutination* / drug effects
  • Humans
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology
  • Protein Binding
  • SARS-CoV-2* / drug effects
  • SARS-CoV-2* / metabolism
  • Spike Glycoprotein, Coronavirus* / chemistry
  • Spike Glycoprotein, Coronavirus* / metabolism

Substances

  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Benzothiazoles
  • Amyloid
  • benzothiazole
  • Peptide Fragments