Interactions between ibuprofen, ACE2, renin‐angiotensin system, and spike protein in the lung. Implications for COVID‐19

An increase in ACE2 activity is essential to balance the tissue renin-angiotensin system (RAS) against the inflammatory response (see Figure S1), and several recent studies have emphasized the pivotal role of tissue RAS in severity of COVID-19.2 Adversely, upregulation of ACE2, as viral entry receptor, may increase cell infection. In healthy adult rats, treatment with ibuprofen (40 mg/kg) significantly increased lung ACE2 expression and enzymatic activity, and increased the expression of anti-inflammatory RAS axis receptors (Mas and angiotensin type 2; AT2); furthermore, ibuprofen induced a significant decrease in proinflammatory AT1 receptor expression (Figure 1A–C). [...]we observed that TRPRSS2 activity significantly increased in pneumocytes treated with spike protein in comparison with untreated control pneumocytes, and TMPRSS2 activity was significantly reduced by pretreatment with ibuprofen (Figure 3O).