General Information:

Id: 11,821 (click here to show other Interactions for entry)
Diseases: COVID-19
Mammalia
review
Reference: Kai H and Kai MInteractions of coronaviruses with ACE2, angiotensin II, and RAS inhibitors-lessons from available evidence and insights into COVID-19 [PMID: 32341442]

Interaction Information:

Comment it has been shown that angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS-CoV-2 infection.
Formal Description
Interaction-ID: 116756

environment

SARS-CoV-2

interacts (colocalizes) with

gene/protein

ACE2

Drugbank entries Show/Hide entries for ACE2
Comment ACE2 degrades angiotensin II to generate angiotensin 1-7, which activates the mas oncogene receptor that negatively regulates a variety of angiotensin II actions mediated by angiotensin II type 1 receptor (AT1R).
Formal Description
Interaction-ID: 116757

gene/protein

ACE2

decreases_quantity of

gene/protein

Angiotensin II

Drugbank entries Show/Hide entries for ACE2
Comment ACE2 degrades angiotensin II to generate angiotensin 1-7, which activates the mas oncogene receptor that negatively regulates a variety of angiotensin II actions mediated by angiotensin II type 1 receptor (AT1R).
Formal Description
Interaction-ID: 116758

gene/protein

ACE2

increases_quantity of

gene/protein

Angiotensin (1-7)

Drugbank entries Show/Hide entries for ACE2
Comment Human ACE2 is an established functional receptor by which SARS-CoV enters host target cells. The transmembrane spike glycoprotein (S protein) of SARS-CoV binds to the cellular membrane ACE2; SARS-CoV then attaches to the target cells, followed by SARS-CoV-S protein priming by cellular surface proteases, such as transmembrane protease serine 2 (TMPRSS2), allowing the fusion of viral and cellular membranes and resulting in SARS-CoV entry and replication in the target cell.
Formal Description
Interaction-ID: 116761

environment

SARS-CoV S protein

interacts (colocalizes) with

gene/protein

ACE2

Drugbank entries Show/Hide entries for ACE2
Comment ACE2 knockout greatly reduces viral infection and replication in mice after experimental SARS-CoV infection.
Formal Description
Interaction-ID: 116763

gene/protein

ACE2

affects_activity of

disease

SARS-CoV infection

Drugbank entries Show/Hide entries for ACE2
Comment Experimental SARS-CoV infection induces acute respiratory failure and lung parenchymal injury characterized by alveolar wall thickening, pulmonary vascular hyperpermeability, and inflammatory cell infiltration in mice. After SARS-CoV infection in mice, lung ACE2 protein levels are greatly reduced, while ACE levels are not changed. These findings are consistent with the previous observation that coronaviruses specifically downregulate ACE2 expression in host cells, depending on virus replication. SARS-CoV-induced acute lung injury is remarkably attenuated in ACE2 knockout mice compared with wild-type mice.
Formal Description
Interaction-ID: 116764

disease

SARS-CoV infection

decreases_quantity of

gene/protein

ACE2

in lung
Drugbank entries Show/Hide entries for ACE2
Comment A similar mechanism is proposed for the severe lung injury caused by the avian influenza A virus H5N1, which has spread worldwide in humans with a high mortality rate. After H5N1 virus infection in mice, lung ACE2 expression is downregulated, and serum angiotensin II levels increase. Acute lung injury is augmented by ACE2 knockout in H5N1-infected mice, while the administration of recombinant human ACE2 ameliorates H5N1-induced lung injury in mice.
Formal Description
Interaction-ID: 116768

disease

Influenza A H5N1 infection

decreases_expression of

gene/protein

ACE2

in lung
Drugbank entries Show/Hide entries for ACE2
Comment Several kinds of ARBs (e.g., olmesartan, telmisartan,losartan, and azilsartan) have been shown to increase the mRNA or protein levels of ACE2 in animal models of heart diseases (hypertensive hypertrophy, autoimmune myocarditis, dilated cardiomyopathy, myocardial infarction, and diabetic cardiomyopathy) and chronic kidney disease (hypertensive nephropathy and diabetic nephropathy), as well as normal rat heart and renal vasculature and hypertensive rat aorta (but not the carotid artery). It should be noted that the doses of ARBs and ACEIs used in these animal studies were much greater than those in clinical practice so that the observed effects of these drugs on ACE2 expression and activity could not be extrapolated to clinical situations in humans. Importantly, no clinical data exist regarding the effects of ARBs and ACEIs on human tissue ACE2 expression or activity in vivo.
Formal Description
Interaction-ID: 116771

drug/chemical compound

Angiotensin II type 1 receptor blocker

increases_quantity of

gene/protein

ACE2

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Comment ACEI does not inhibit ACE2 as a pharmacological property.
Formal Description
Interaction-ID: 116774

drug/chemical compound

ACE inhibitor

NOT decreases_activity of

gene/protein

ACE2

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