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.