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

Abstract

There is evidence that amyloidogenic segments in SARS-COV-2 proteins can induce aggregation of -synuclein (S), the main component of brain-located amyloids whose presence is connected with Parkinsons Disease (PD). Using molecular dynamic simulations, we could show in earlier work that SARS-COV-2 protein fragments shift the ensemble of S 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 194FKNIDGYFKI203 (FI10) of the SARS-COV-2 spike protein, and the fragment 54SFYVYSRVK62 (SK9) of the envelope protein, alter the ensemble of -synuclein dimers. Our simulations suggest a differential stabilization of such dimers that would preferentially seed rod-like fibrils over the competing twister-like structures.