Fig. 1 | Signal Transduction and Targeted Therapy

Fig. 1

From: Human recombinant soluble ACE2 (hrsACE2) shows promise for treating severe COVID­19

Fig. 1

Schematic diagram of the renin-angiotensin system and the proposed therapeutic treatment for COVID-19 targeting SARS-CoV-2 viral entry mechanism. (Left) The receptor-binding domain (RBD) of the spike protein from SARS-CoV-2 binds to ACE2, allowing host cell entry and infection. TMPRSS2 indicates transmembrane protease serine 2. (Middle) The physiological role of ACE2 in renin-angiotensin system and its protective effect on organs. The protease renin, an enzyme produced by the juxtaglomerular cells of the kidney, cleaves angiotensinogen (a precursor of angiotensin produced by the liver) to generate angiotensin I. ACE plays an important role in converting angiotensin I into angiotensin II. Angiotensin II may exert some biological functions through angiotensin II receptor type 1 and 2 receptors (AT1R and AT2R), leading to potent vasoconstriction in several organs. Activation of AT1R increases the transmembrane proteinase (ADAM17) activity. Furthermore, tumor necrosis factor-α (TNF-α) activation of its tumor necrosis factor receptor (TNFR) represents another pathway increasing ADAM17 activity. TNF-α along with cytokines released due to SARS-CoV-2 infection can lead to a cytokine storm. ADAM17 cleaves the extracellular juxta-membrane region of ACE2, whether such ACE2 cleavage contributes to SARS pathogenesis is not known yet. ACE2 hydrolyzes Angiotensin II to the vasodilator Angiotensin 1–7, which binds the Mas receptor and plays a protective role in several organs. The balance between ACE/Ang II/AT1R and ACE2/Ang 1–7/MasR is vital for maintaining normal health. (Right) According to recent studies, increasing of hrsACE2 at tissue sites can effectively compete with the endogenous ACE2 and limits SARS-CoV-2 entrance into the host cells and decreases angiotensin II levels.1,4 Significantly, hrsACE2 injection did not reduce the generation of anti-SARS-CoV-2 IgA and IgG antibodies

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