Fig. 1

The carboxypeptidase angiotensin-converting enzyme 2 (ACE2) converts angiotensin (Ang) I into Ang-(1–9) and Ang II into Ang-(1–7) and (panel a), yet is not blocked by ACE inhibitors, which prevent the conversion of Ang I to Ang II. As depicted in (panel b), ACE2 also binds and internalizes SARS-Cov-2, after priming by the serine protease transmembrane protease, serine 2 (TMPRSS2). Shedding of membrane-bound ACE2 by a disintegrin and metalloprotease 17 (ADAM17) results in the occurrence of soluble (s) ACE2, which can no longer mediate SARS-Cov-2 entry, and which might even prevent such entry by keeping the virus in solution. Ang II, via its type 1 receptor (AT₁R), upregulates ADAM17, and AT₁R blockers (ARBs) would prevent this. Ibuprofen has been suggested to increase ACE2, possibly via inhibition of cyclooxygenases (COXs) and activation of Peroxisome Proliferator-Activated Receptor gamma (PPAR-γ). Redrawn after [4]