The Effect of SARS-COV-2 Protein Fragments on the Dimerization of α-Synuclein

There is evidence that amyloidogenic segments in SARS-COV-2 proteins can induce aggregation of α-synuclein (αS), the main component of brain-located amyloids whose presence is connected with Parkinson’s Disease (PD). Using molecular dynamic simulations, we could show in earlier work that SARS-COV-2 protein fragments shift the ensemble of αS chains toward more aggregation-prone conformations. However, the mechanism by which these chains assemble into fibrils, the presumed neurotoxic agent in PD, is not clear. The first step on that route are dimers. For this reason, we have now, using again molecular dynamics simulations, studied how the fragment ₁₉₄ FKNIDGYFKI ₂₀₃ (FI10) of the SARS-COV-2 spike protein, and the fragment ₅₄ SFYVYSRVK ₆₂ (SK9) of the envelope protein, alter the ensemble of α-synuclein dimers. Our simulations suggest a differential stabilization of such dimers that would preferentially seed rod-like fibrils over the competing twister-like structures.