The recent emergence of the novel coronavirus (SARS-CoV-2/COVID-19) has quickly become a worldwide threat to health, causes severe respiratory syndrome in human. SARS-Cov-2 likely facilitates entry into cells via Angiotensin-converting enzyme 2 (ACE2) expressed by pneumocytes, pulmonary macrophages, heart, kidneys and intestine. The physiological role of ACE2 is in the maturation of angiotensin, controlling the blood pressure. However, a comparison of the amino acid sequence of the receptor binding domain of SARS-CoV-2 (COVID-19) and SARS-CoV (SARS) suggest that, like SARS-CoV, SARS-CoV-2 facilitates cell entry via ACE2 receptors (Hoffman et al., 2020; Wan et al., 2020). Treatment with ACE2-stimulating drugs (ACE-Is) may increase the risk of developing severe or fatal SARs-CoV-2 in conditions such as hypertension, diabetes, COPD, CHD and cerebrovascular disease (Fang et al., 2020).Patients commonly present a cytokine storm syndrome (CSS). CSS is characterized by an excessive or uncontrolled release of proinflammatory cytokines that could be triggered by a wide variety of infectious and noninfectious diseases. The over production of inflammatory factors, such as TNFa, IL-6, IFNy, IL-1b have been described to increased risk of vascular permeability and leads to peripheral organ failure Previous reports have demonstrated that ACE2 is upregulated in hypoxic conditions via an unknown (HIF-1± independent) mechanism. In pulmonary artery smooth muscle cells (PASMCs), ACE2 is initially upregulated in hypoxic conditions with mRNA and protein expression peaking at 12 and 24hours respectively. This is followed by downregulation via HIF-1±- mediated ACE upregulation and resulting ANGII accumulation (Zhang et al., 2009). However, its necessary investigate the profile of cytokines that is produced during the covid10 infection. Nevertheless, a central question remains if Does hypoxia upregulate ACE2 expression in mouse lung tissue via a HIF-2±- dependent mechanism? In addition, if ACE2 is a HIF target gene, there are two classes of compounds (PHIs and PT compounds) are undergoing clinical trials with promising results in HIF inhibition which could be used for treatment.
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