SARS-CoV-2 spike protein reduces burst activities in neurons measured by micro-electrode arrays.

Abstract

The authors extracted the whole-brain neurons from the newborn P1 mice and plated them on multiwell MEAs and administered purified recombinant spike proteins (both S1 and S2 subunits) from the SARS-CoV-2 virus. The signals from the MEAs were transmitted from an amplifier to a high-performance computer for recording and analysis using an in-house developed algorithm to quantify neuronal phenotypes. Primary among the phenotypic features analyzed, we discovered that neuronal treatment with spike 1 protein (S1) protein from SARS-CoV-2 decreased the mean burst numbers observed on each electrode, an effect that could be rescued with an anti-S1 antibody. Conversely, this mean burst number decrease was not observed with spike 2 protein (S2) treatment. Finally, our data strongly suggest that the receptor binding domain of S1 is responsible for the reduction in neuronal burst activity. Overall, our results strongly indicate that spike proteins may play an important role in altering neuronal phenotypes, specifically the burst patterns, when neurons are exposed during early development.