Multidirectional Effects of SARS-CoV-2 Coronavirus Proteins on Amyloid Transformation of Alpha-Synuclein

Parkinson's disease is associated with amyloid aggregation of alpha-synuclein, which could be affected by the proteins of the SARS-CoV-2 coronavirus, possibly accelerating and provoking neurodegeneration. The purpose of this work was to compare the effects of the N-protein and the receptor binding domain (RBD) of the S protein on fibrillization of the alpha-synuclein preparation produced using an original technique that excludes presence of non-native forms of alpha-synuclein that alter kinetics of the process. Presence of an elongated form of alpha-synuclein in the previously studied protein preparations is associated with the erroneous reading of the rare for E. coli TGA stop codon in the pET33b(+) expression plasmid as tryptophan, which led to the continued translation to the next stop codon. To prevent this effect, a new plasmid design was suggested with replacement of the original stop codon with a double stop codon TAA, which made it possible to obtain a homogeneous protein preparation without the admixture of alpha-synuclein with increased molecular weight. It has been shown that the N-protein is able to accelerate alpha-synuclein fibrillization, while the RBD of the S protein inhibits aggregation. According to the electron microscopy data, structure of the fibrils formed in the presence of viral proteins is also different. The obtained data are important for understanding the mechanisms of development of post-covid synucleinopathies, as well as consequences of vaccination with the viral proteins.