Effect of an Amyloidogenic SARS-COV-2 Protein Fragment on α-Synuclein Monomers and Fibrils

Aggregates of alpha-synuclein are thought to be the disease-causing agent in Parkinson's disease. Various case studies have hinted at a correlation between COVID-19 and the onset of Parkinson's disease. For this reason, we use molecular dynamics simulations to study whether amyloidogenic regions in SARS-COV-2 proteins can initiate and modulate aggregation of alpha-synuclein. As an example, we choose the nine-residue fragment SFYVYSRVK (SK9), located on the C-terminal of the envelope protein of SARS-COV-2. We probe how the presence of SK9 affects the conformational ensemble of alpha-synuclein monomers and the stability of two resolved fibril polymorphs. We find that the viral protein fragment SK9 may alter alpha-synuclein amyloid formation by shifting the ensemble toward aggregation-prone and preferentially rod-like fibril seeding conformations. However, SK9 has only a small effect on the stability of pre-existing or newly formed fibrils. A potential mechanism and key residues for potential virus-induced amyloid formation are described.

Automated summary

This study investigates the role of amyloidogenic regions in SARS-COV-2 proteins in the aggregation of alpha-synuclein. Using molecular dynamics simulations, the authors find that a viral protein fragment, SK9, may promote alpha-synuclein amyloid formation by shifting its conformational ensemble. However, SK9 has little effect on the stability of pre-existing or newly formed fibrils. The study provides insights into potential virus-induced amyloid formation.