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Updated: Jan 16, 2026
Saccharomyces cerevisiae Models of Alzheimer's Disease to Screen Genes, Mutations, and Chemicals Affecting Amyloid Beta Production by γ-Secretase
Published on: June 24, 2025
Modulation of Aβ1-42 Aggregation by a SARS-CoV-2 Protein Fragment
Malinda B Premathilaka1, Ulrich H E Hansmann1
1Department of Chemistry & Biochemistry, University of Oklahoma, Norman, Oklahoma 73019, United States.
Abstract:
A number of studies have pointed out the possibility that SARS-CoV-2 infections could trigger amyloid diseases such as Parkinson's disease or type II diabetes. In the present study, we probe this question for Alzheimer's disease, which is connected with the presence of amyloids rich in Aβ peptides. For this purpose, we study, by way of molecular dynamics simulations, the interaction between the fragment FKNIDGYFKI of the Spike protein with an Aβ1-42 monomer and two fibril models, one patient-derived and one synthetic. We find that the viral protein fragment appears to shift the ensemble of monomer conformations toward more aggregation-prone ones, and that fibril polymorphs found in patients with Alzheimer's disease appear to be more stabilized than synthetic fibrils. We discuss commonalities and differences in the modulation of amyloid formation by the viral protein fragments by comparing our results with previous studies of other amyloid-forming proteins.
Insights
The SARS-CoV-2 Spike protein may promote Alzheimer's disease by interacting with amyloid-beta peptides. This interaction shifts proteins toward aggregation, potentially worsening amyloid pathology in Alzheimer's disease.
Area of Science:
- Neuroscience
- Infectious Diseases
- Biochemistry
Background:
- Emerging evidence suggests SARS-CoV-2 infection may trigger amyloid diseases.
- Alzheimer's disease is characterized by amyloid-beta (Aβ) peptide aggregation.
- The link between SARS-CoV-2 and Alzheimer's disease requires further investigation.
Purpose of the Study:
- To investigate the interaction between a SARS-CoV-2 Spike protein fragment and Aβ peptides.
- To determine if SARS-CoV-2 can modulate Aβ aggregation relevant to Alzheimer's disease.
Main Methods:
- Molecular dynamics simulations were employed.
- The study focused on the interaction between the Spike protein fragment (FKNIDGYFKI) and Aβ1-42 monomers and fibrils.
- Patient-derived and synthetic Aβ fibril models were utilized.
Main Results:
- The viral protein fragment shifts Aβ monomer conformations towards aggregation-prone states.
- Patient-derived Alzheimer's disease Aβ fibril polymorphs were more stabilized by the viral fragment than synthetic fibrils.
- The study identified specific interactions modulating amyloid formation.
Conclusions:
- SARS-CoV-2 Spike protein interactions may promote Aβ aggregation, potentially contributing to Alzheimer's disease pathogenesis.
- Viral protein fragments can influence amyloid formation pathways.
- Further research is needed to understand the full implications of these interactions for neurodegenerative diseases.
