New Viral Diseases and New Possible Remedies by Means of the Pharmacology of the Renin-Angiotensin System

Figure 3

SARS-CoV-2 causes cell membrane ACE2 depletion through cellular internalization and subsequent proteasomal degradation once the enzyme is bound to infecting virions, but also through ADAM-17 upregulation. Ang II contributes to ADAM-17 upregulation. Upregulated ADAM-17 causes shedding of ACE2, interleukin-4, IFNγ, and TNF-α into extracellular fluids. In turn, free interleukin-4 and IFNγ further downregulate ACE2 cellular expression, while free TNF-α starts the inflammatory cascade.