Does the SARS-CoV-2 Spike Receptor-Binding Domain Hamper the Amyloid Transformation of Alpha-Synuclein after All?

Interactions of key amyloidogenic proteins with SARS-CoV-2 proteins may be one of the causes of expanding and delayed post-COVID-19 neurodegenerative processes. Furthermore, such abnormal effects can be caused by proteins and their fragments circulating in the body during vaccination. The aim of our work was to analyze the effect of the receptor-binding domain of the coronavirus S-protein domain (RBD) on alpha-synuclein amyloid aggregation. Molecular modeling showed that the predicted RBD complex with monomeric alpha-synuclein is stable over 100 ns of molecular dynamics. Analysis of the interactions of RBD with the amyloid form of alpha-synuclein showed that during molecular dynamics for 200 ns the number of contacts is markedly higher than that for the monomeric form. The formation of the RBD complex with the alpha-synuclein monomer was confirmed immunochemically by immobilization of RBD on its specific receptor ACE2. Changes in the spectral characteristics of the intrinsic tryptophans of RBD and hydrophobic dye ANS indicate an interaction between the monomeric proteins, but according to the data of circular dichroism spectra, this interaction does not lead to a change in their secondary structure. Data on the kinetics of amyloid fibril formation using several spectral approaches strongly suggest that RBD prevents the amyloid transformation of alpha-synuclein. Moreover, the fibrils obtained in the presence of RBD showed significantly less cytotoxicity on SH-SY5Y neuroblastoma cells.