Role of ACE2 in COVID-19].

Yumiko Imai

Nihon yakurigaku zasshi. Folia pharmacologica Japonica 2022

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In the renin-angiotensin system (RAS), angiotensin II (AngII) converted by angiotensin converting enzyme (ACE) exerts a strong physiological activity via the AT1 receptor (AT1R). Thus, the ACE-AngII-AT1R axis positively regulates RAS. On the other hand, angiotensin converting enzyme 2 (ACE2) is known to negatively regulate RAS by degrading AngII into angiotensin 1-7 (Ang1-7). In the acute respiratory distress syndrome (ARDS), which is characterized by pulmonary hyperinflammation, the AngII-AT1R axis acts to exacerbate ARDS and the ACE2-AT2R axis acts protectively. More recently, ACE2 has been shown to be a receptor for SARS-CoV, the causative virus of severe acute respiratory syndrome (SARS), and SARS-CoV2, the causative virus of the 2019 coronavirus infection (COVID-19). Therefore, inhibition of the binding between ACE2 and virus spike protein is a drug discovery target for antiviral drugs against SARS-CoV and SARS-CoV2. In addition, when SARS and COVID-19 become severe, ARDS with cytokine storm is occured. We reported that soluble ACE2 protein and microbial-derived ACE2 like enzyme suppress pulmonary hyperinflammation due to SARS and COVID-19, respectively. In addition, it has been reported that the ACE2-soluble protein has an effect of suppressing the establishment of infection by inhibiting the binding between SARS-CoV2 and the cell membrane surface ACE2. Here, we describe the role of ACE2 in the pathophysiology of SARS/COVID-19 from the perspectives of inhibiting the progression to ARDS by suppressing pulmonary inflammation and suppressing the replication of the virus by inhibiting the binding of ACE2 to the spike protein.