Cathepsin L, transmembrane peptidase/serine subfamily member 2/4, and other host proteases in COVID-19 pathogenesis – with impact on gastrointestinal tract

Figure 1 Alternations in spike proteins conformation upon binding to ACE 2. Spike S1 subunit contains receptor binding domain, that has to change from “down-conformation” state to “up-conformation” state to be accessible for ACE2. Changes in S1 subunit trigger conformational changes in S2 subunit, causing exposition of hydrophobic domain, changing it from “pre-fusion” to “post-fusion” state. This enables fusion of the virus with host membrane (after Zhu et al[7]).

Figure 2 Two modes of virus entry. A: Receptor-mediated endocytosis of severe acute respiratory syndrome coronavirus-2. After binding to ACE2 and formation of endosome, lysosomal cathepsins activate spike protein, which leads to the release of the viral RNA into host cell. B: Membrane fusion mechanism - priming of the spike proteins is mediated by transmembrane peptidase/serine subfamily member 2/4, which leads to fusion of viral and host membranes and release of the viral RNA into host cell.