Figure 4.

Inhibition of SARS-CoV-2 infection and processing by fibrinolysis pathway-associated serpins. SARS-CoV-2 entry is dependent on proteolytic processing of the spike protein in order to engage the ACE2 receptor and internalize. Processing of the spike protein is performed primarily by TMPRSS2 and Furin. PAI-1 and A1AT are known inhibitors of TMPRSS2 and experimental evidence demonstrates that A1AT can inhibit SARS-CoV-2 infection in vitro. Based on similarities in inhibition properties, it may be predicted that Serp-1 will also inhibit TMPRSS2 with similar results. Furin has both an extracellular and intracellular role in the SARS-CoV-2 life cycle and there is evidence for extracellular furin inhibition by A1AT and A1AT variants (Portland and α-PDX) as well as endothelial PN-1, and for intracellular furin inhibition by PAI-1.