The effect of SARS-COV-2 Infections on Amyloid Formation of Serum Amyloid A

Jana, Asis K.; Greenwood, Augustus B.; Hansmann, Ulrich H. E.

A marker for the severeness and disease progress of COVID-19 is overexpression of serum amyloid A (SAA) to levels that in other diseases are associated with a risk for SAA amyloidosis. This secondary illness is characterized by formation and deposition of SAA amyloids in blood vessels, causing inflammation, thrombosis and sometimes organ failure, with symptoms resembling the multisystem inflammatory syndrome (MIS) observed in some COVID-19 survivors. Hence, in order to understand better the danger of SAA amyloidosis in the context of COVID-19 we have used molecular dynamic simulations to study the effect of a SARS-COV-2 protein segment on SAA amyloid formation. We find that presence of the nine-residue segment SK9, located on the Envelope protein, increases the propensity for SAA fibril formation by three mechanisms: it reduces the stability of the lipid-transporting hexamer shifting the equilibrium toward monomers, it increases the frequency of aggregation-prone configurations in the resulting chains, and it raises the stability of SAA fibrils. Our results therefore suggest that SAA amyloidosis-related pathologies are a long-term risk of SARS-COV-2 infections.