Fig. 1.

Target cell infection by SARS-CoV-2 and contribution of ACE2. SARS-CoV-2 uses the ACE2 receptors in target cells, for its entry and infection. ACE2 is a catalytically active protective enzyme, which in normal conditions degrades angiotensin-II peptides. After the attachment of the virus, it enters into the cell and then its genome starts to replication and production of virus proteins, and ACE2 loses its catalytic activity. Upon virus binding to the membrane-anchored ACE2 receptor, ADAM-17 enzyme mediates ACE2 catalytic shedding and release of the sACE2. During this catalytic shedding, the release of some proinflammatory cytokines such as IL-1β and TNFα due to the activity of the TNFα-converting enzyme may also occur. The sACE2 maintains its ability for binding to viral spike protein, so its presence could intercept SARS-CoV-2 and prevents interaction with cell surface ACE2 receptors. Moreover, intracellular virus replication and accumulation of ACE2 substrate (Ang II) activates cell signaling cascades, which may lead to activation of innate immunity receptors by the production of INF-α/β and proinflammatory cytokines. Subsequently, the process of virus propagation and shedding of the infected cells may result in cell damage and apoptosis.