In order to develop effective drugs and vaccines, one needs to efficiently simulate SARS-CoV-2 spike receptor binding domain (RBD) mutations and identify high-risk variants.

SARS-CoV-2 enters cells through the binding of its spike receptor-binding domain (RBD) to the human angiotensin-converting enzyme 2 (ACE2) receptor in concert with accessory receptors/molecules that facilitate viral attachment, internalization, and fusion.

Although the mechanism by which SARS-CoV-2 enters the brain is still unclear, the possibility of direct entry through the olfactory nerve tract and entry into the brain through the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) via blood circulation is indicated.

The angiotensin-converting enzyme (ACE) gene contains an insertion/deletion (I/D) polymorphism that leads to a higher serum ACE level which is associated with several diseases and also with a high mortality rate in SARS.

However, even given that COVID-19 pathophysiology may be driven by an imbalance in the renin-angiotensin system (RAS), we were still far from understanding the complexity of the mechanisms which are controlled by ACE2 in different cell types.

Antibodies to C19 nucleocapsid (N), receptor-binding domain (RBD), spike 1 (S1), and spike 2 (S2) were measured.

The spike protein on the virus surface interacts with the human angiotensin-converting enzyme (ACE2) via the so-called receptor binding domain (RBD), facilitating virus entry.

We additionally explored the hypothesis that SARS-CoV-2 favors the internalization of membrane ACE2 receptors generating an imbalance of the renin-angiotensin-aldosterone system (RAAS), increasing the activity of angiotensin II (ANG-II), disintegrin, and metalloproteinase 17 domain (ADAM17/TACE), eventually modulating the integration of afferents reaching the NTS from baroreceptors and promoting increased blood pressure.

We used logistic regression to estimate the odds ratio (OR) and the 95% confidence interval (CI) of COVID-19 severity in patients prescribed Angiotensin Receptor Blockers (ARB) versus those not prescribed ARB.

The parallel evaluation of a second immune-stimulating fusion candidate, Granulocyte-macrophage colony-stimulating factor (GM-CSF), induced high neutralizing responses in select animals but narrowly missed achieving significance at the group level.