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 dynamics simulations, we showed 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 agents in PD, is not clear. The first step on that route is the formation of dimers. For this reason, we have now, using again molecular dynamics simulations, studied how the fragment 194FKNIDGYFKI203 (FI10) of the SARS-COV-2 spike protein and the fragment 54SFYVYSRVK62 (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.