SerpinB3/Protease Activated Receptor-2 Axis Is Essential for SARS CoV-2 Infection

: Recent research has proposed several host factors required for SARS-CoV-2 infection and involved in the inflammatory response. Among these, members of the human serpin family and PAR2 have been suggested to play a relevant role. As it has been shown that one of the multiple activities of protease inhibitor SerpinB3 is the activation of PAR2, we have modulated the expression of these two molecules on both human bronchial and hepatic cells and assessed cell surface Spike binding and SARS-CoV-2 infectivity. Our findings indicate that both SerpinB3 and PAR2 play a pivotal role in viral infection and downregulate the expression of interferon-γ, a cytokine with a well-known antiviral effect. These results underscore the potential of the SerpinB3-PAR2 axis as a target for antiviral therapy and provide support for addressing serpins as targets for this purpose.