4. ACE2 and SARS-CoV-2 Spike protein
Spike protein (S) is a viral protein, it is composed of two functional subunits, including the S1 and S2 subunits. The S1 subunit consists of N-terminal domain and receptor binding domain (RBD). The function of S1 is bind to the receptor on host cell. The function of S2 is to fuse the membranes of SARS-CoV-2 and host cells [31]. RBD is responsible for interacting with the angiotensin-converting enzyme 2 (ACE2) receptor on the surface of human host-cells.
The angiotensin-converting enzyme 2 (ACE2) receptor is used by the virus as the entry point in human cells [32,33]. SARS-CoV-2 infection is initiated by virus binding to the ACE2 cell-surface receptors [34-37], followed by fusion of the virus and cell membranes to release the virus genome into the host cell. Both receptor binding and membrane fusion are mediated by the virus spike glycoprotein [38]. Some autor describe a sequential ACE2-binding events until reaching the fully open state, three-ACE2-bound spike protein [39]. Interestingly, despite the higher affinity of the SARS-CoV-2 receptor binding protein (RBD) for ACE2 compared with the SARS-CoV RBD, the SARS-CoV-2 S protein trimer does not bind ACE2 as efficiently as does the SARS-CoV S protein trimer [40,41]. It is interesant to point that the ACE2 modulation can alter the ROS generation [42], which is one of the characteristic molecular of the neurodegenerative diseases.