The SIGnaling Network
Open Resource

Pathway ID: SIGNOR-SCAAEView in NDEx

Description: SARS-CoV2 engages angiotensin-converting enzyme 2 (ACE2) as a receptor for viral attachment to the target cell surface. Entry requires priming of the S protein by the cellular serine protease TMPRSS2 and the endosomal cysteine proteases cathepsin B and L (CatB/L), which cleave S protein at the S1/S2 sites, allowing specific interaction between S1 and ACE2 receptor. When SARS-CoV2 binds ACE2, it is internalized by clathrin-dependent endocytosis or by direct membrane fusion of viral and cellular membranes. Binding of the Spike protein to ACE2 suppresses the expression of the receptor by increasing internalization and shedding from the cell surface. The decreased expression of ACE2 and the consequent reduction of Ang1–7 leads to the downregulation of the Ang1–7-receptor Mas1. Mas1 modulates the inflammatory response and activates a signalling cascade regulating the IRF3-mediated stimulation of the immune response.

Curated by: Marta Iannuccelli