Fig. 3.

The protease/antiprotease balance regulates influenza A virus (IAV) infection and can be modulated by SFN supplementation. 1: For entry into target host cells, the hemagglutinin (HA) protein on the IAV virion must be proteolytically cleaved from HA0 (purple) into fusoactive HA1 and HA2 proteins (blue). 2: Respiratory serine proteases such as TMPRSS2 (TM), the human airway trypsin-like protease (HAT), and matriptase have been implicated in HA activation and IAV infection, which are likely to strain specific. Although antiproteases such as SLPI inhibit serine protease activity and protect against IAV infection, it remains unknown what HA-activating protease is inhibited by SLPI and how SLPI mediates these effects. 3: Lastly, SFN supplementation can be used to increase SLPI secretion, reduce TMPRSS2 secretion, and decrease viral entry and downstream IAV infection.