PMC:7190487 / 898-2873 JSONTXT

{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T6","span":{"begin":213,"end":223},"obj":"Body_part"},{"id":"T7","span":{"begin":262,"end":270},"obj":"Body_part"},{"id":"T8","span":{"begin":650,"end":654},"obj":"Body_part"},{"id":"T9","span":{"begin":937,"end":951},"obj":"Body_part"},{"id":"T10","span":{"begin":952,"end":969},"obj":"Body_part"},{"id":"T11","span":{"begin":964,"end":969},"obj":"Body_part"},{"id":"T12","span":{"begin":999,"end":1005},"obj":"Body_part"},{"id":"T13","span":{"begin":1020,"end":1025},"obj":"Body_part"},{"id":"T14","span":{"begin":1658,"end":1661},"obj":"Body_part"}],"attributes":[{"id":"A6","pred":"fma_id","subj":"T6","obj":"http://purl.org/sig/ont/fma/fma305853"},{"id":"A7","pred":"fma_id","subj":"T7","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A8","pred":"fma_id","subj":"T8","obj":"http://purl.org/sig/ont/fma/fma7195"},{"id":"A9","pred":"fma_id","subj":"T9","obj":"http://purl.org/sig/ont/fma/fma70317"},{"id":"A10","pred":"fma_id","subj":"T10","obj":"http://purl.org/sig/ont/fma/fma66772"},{"id":"A11","pred":"fma_id","subj":"T11","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A12","pred":"fma_id","subj":"T12","obj":"http://purl.org/sig/ont/fma/fma7203"},{"id":"A13","pred":"fma_id","subj":"T13","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A14","pred":"fma_id","subj":"T14","obj":"http://purl.org/sig/ont/fma/fma24890"}],"text":"2.1 Metformin-AMPK-ACE2-SARS-CoV-2\nThe juggernaut virus, SARS-CoV-2, that has led to the deaths of over 1.7 lakh people across the world uses angiotensin-converting enzyme 2 (ACE2) as its receptor. It enters the human body through interaction between its spike proteins (S1) and the N-terminal region of ACE2 [4], [5]. The receptor binding domain (RBD) of the virus binds with the protease domain (PD) of the ACE2 receptor and forms an RBD-PD complex [4].\nAcute Respiratory Distress Syndrome (ARDS) is one of the commonest complications developing in patients with COVID-19 [6]. There have been animal studies that have implicated ACE2 in the acute lung injury (ALI) caused due to SARS-CoV [4]. It has been hypothesized that ACE2 causes ALI by bringing about autophagy through the AMPK/mTOR pathway [7]. AMPK has been shown to increase the expression of ACE2 as well as to increase its stability by phosphorylating ACE2 Ser680 in human umbilical vein endothelial cells (HUVECs) and human embryonic kidney 293 (HEK293T) cells [8].\nSince metformin works through AMPK activation, which leads to phosphorylation of ACE2 [8], we can consider that theoretically this addition of a phosphate group (PO4 −3) would bring about conformational and functional changes in the ACE2 receptor [9]. This could lead to decreased binding with SARS-CoV-2 RBD due to steric hindrance by the addition of a large sized PO4 −3 molecule.\nNonetheless, once the virus is inside, there is a downregulation of ACE2 receptors. This in turn leads to an imbalance in the renin-angiotensin-aldosterone system (RAS) promoting the deleterious effects of its pro-inflammatory and pro-fibrotic arm, further giving rise to the lethal cardio-pulmonary complications [10]. By upregulating ACE2, the imbalance in RAS could be averted. Hence, metformin would not only prevent the entry of SARS-CoV-2 as described above, but also prevent the detrimental sequelae by causing activation of ACE2 through AMPK-signalling."}

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T1","span":{"begin":650,"end":654},"obj":"Body_part"},{"id":"T2","span":{"begin":937,"end":951},"obj":"Body_part"},{"id":"T3","span":{"begin":947,"end":951},"obj":"Body_part"},{"id":"T4","span":{"begin":999,"end":1005},"obj":"Body_part"},{"id":"T5","span":{"begin":1658,"end":1661},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/UBERON_0002066"},{"id":"A3","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/UBERON_0001638"},{"id":"A4","pred":"uberon_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/UBERON_0002113"},{"id":"A5","pred":"uberon_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/UBERON_0001460"}],"text":"2.1 Metformin-AMPK-ACE2-SARS-CoV-2\nThe juggernaut virus, SARS-CoV-2, that has led to the deaths of over 1.7 lakh people across the world uses angiotensin-converting enzyme 2 (ACE2) as its receptor. It enters the human body through interaction between its spike proteins (S1) and the N-terminal region of ACE2 [4], [5]. The receptor binding domain (RBD) of the virus binds with the protease domain (PD) of the ACE2 receptor and forms an RBD-PD complex [4].\nAcute Respiratory Distress Syndrome (ARDS) is one of the commonest complications developing in patients with COVID-19 [6]. There have been animal studies that have implicated ACE2 in the acute lung injury (ALI) caused due to SARS-CoV [4]. It has been hypothesized that ACE2 causes ALI by bringing about autophagy through the AMPK/mTOR pathway [7]. AMPK has been shown to increase the expression of ACE2 as well as to increase its stability by phosphorylating ACE2 Ser680 in human umbilical vein endothelial cells (HUVECs) and human embryonic kidney 293 (HEK293T) cells [8].\nSince metformin works through AMPK activation, which leads to phosphorylation of ACE2 [8], we can consider that theoretically this addition of a phosphate group (PO4 −3) would bring about conformational and functional changes in the ACE2 receptor [9]. This could lead to decreased binding with SARS-CoV-2 RBD due to steric hindrance by the addition of a large sized PO4 −3 molecule.\nNonetheless, once the virus is inside, there is a downregulation of ACE2 receptors. This in turn leads to an imbalance in the renin-angiotensin-aldosterone system (RAS) promoting the deleterious effects of its pro-inflammatory and pro-fibrotic arm, further giving rise to the lethal cardio-pulmonary complications [10]. By upregulating ACE2, the imbalance in RAS could be averted. Hence, metformin would not only prevent the entry of SARS-CoV-2 as described above, but also prevent the detrimental sequelae by causing activation of ACE2 through AMPK-signalling."}

{"project":"LitCovid-PD-MONDO","denotations":[{"id":"T5","span":{"begin":25,"end":33},"obj":"Disease"},{"id":"T6","span":{"begin":58,"end":66},"obj":"Disease"},{"id":"T7","span":{"begin":457,"end":492},"obj":"Disease"},{"id":"T8","span":{"begin":463,"end":492},"obj":"Disease"},{"id":"T9","span":{"begin":494,"end":498},"obj":"Disease"},{"id":"T10","span":{"begin":566,"end":574},"obj":"Disease"},{"id":"T11","span":{"begin":644,"end":661},"obj":"Disease"},{"id":"T13","span":{"begin":655,"end":661},"obj":"Disease"},{"id":"T14","span":{"begin":663,"end":666},"obj":"Disease"},{"id":"T15","span":{"begin":682,"end":690},"obj":"Disease"},{"id":"T16","span":{"begin":738,"end":741},"obj":"Disease"},{"id":"T17","span":{"begin":1325,"end":1333},"obj":"Disease"},{"id":"T18","span":{"begin":1848,"end":1856},"obj":"Disease"}],"attributes":[{"id":"A5","pred":"mondo_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A7","pred":"mondo_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/MONDO_0006502"},{"id":"A8","pred":"mondo_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/MONDO_0009971"},{"id":"A9","pred":"mondo_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/MONDO_0006502"},{"id":"A10","pred":"mondo_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A11","pred":"mondo_id","subj":"T11","obj":"http://purl.obolibrary.org/obo/MONDO_0006502"},{"id":"A12","pred":"mondo_id","subj":"T11","obj":"http://purl.obolibrary.org/obo/MONDO_0015796"},{"id":"A13","pred":"mondo_id","subj":"T13","obj":"http://purl.obolibrary.org/obo/MONDO_0021178"},{"id":"A14","pred":"mondo_id","subj":"T14","obj":"http://purl.obolibrary.org/obo/MONDO_0006502"},{"id":"A15","pred":"mondo_id","subj":"T15","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A16","pred":"mondo_id","subj":"T16","obj":"http://purl.obolibrary.org/obo/MONDO_0006502"},{"id":"A17","pred":"mondo_id","subj":"T17","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A18","pred":"mondo_id","subj":"T18","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"}],"text":"2.1 Metformin-AMPK-ACE2-SARS-CoV-2\nThe juggernaut virus, SARS-CoV-2, that has led to the deaths of over 1.7 lakh people across the world uses angiotensin-converting enzyme 2 (ACE2) as its receptor. It enters the human body through interaction between its spike proteins (S1) and the N-terminal region of ACE2 [4], [5]. The receptor binding domain (RBD) of the virus binds with the protease domain (PD) of the ACE2 receptor and forms an RBD-PD complex [4].\nAcute Respiratory Distress Syndrome (ARDS) is one of the commonest complications developing in patients with COVID-19 [6]. There have been animal studies that have implicated ACE2 in the acute lung injury (ALI) caused due to SARS-CoV [4]. It has been hypothesized that ACE2 causes ALI by bringing about autophagy through the AMPK/mTOR pathway [7]. AMPK has been shown to increase the expression of ACE2 as well as to increase its stability by phosphorylating ACE2 Ser680 in human umbilical vein endothelial cells (HUVECs) and human embryonic kidney 293 (HEK293T) cells [8].\nSince metformin works through AMPK activation, which leads to phosphorylation of ACE2 [8], we can consider that theoretically this addition of a phosphate group (PO4 −3) would bring about conformational and functional changes in the ACE2 receptor [9]. This could lead to decreased binding with SARS-CoV-2 RBD due to steric hindrance by the addition of a large sized PO4 −3 molecule.\nNonetheless, once the virus is inside, there is a downregulation of ACE2 receptors. This in turn leads to an imbalance in the renin-angiotensin-aldosterone system (RAS) promoting the deleterious effects of its pro-inflammatory and pro-fibrotic arm, further giving rise to the lethal cardio-pulmonary complications [10]. By upregulating ACE2, the imbalance in RAS could be averted. Hence, metformin would not only prevent the entry of SARS-CoV-2 as described above, but also prevent the detrimental sequelae by causing activation of ACE2 through AMPK-signalling."}

{"project":"LitCovid-PD-CLO","denotations":[{"id":"T6","span":{"begin":51,"end":56},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T7","span":{"begin":75,"end":78},"obj":"http://purl.obolibrary.org/obo/CLO_0051582"},{"id":"T8","span":{"begin":213,"end":218},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},{"id":"T9","span":{"begin":272,"end":274},"obj":"http://purl.obolibrary.org/obo/CLO_0050050"},{"id":"T10","span":{"begin":311,"end":317},"obj":"http://purl.obolibrary.org/obo/CLO_0053799"},{"id":"T11","span":{"begin":361,"end":366},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T12","span":{"begin":596,"end":602},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_33208"},{"id":"T13","span":{"begin":650,"end":654},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"T14","span":{"begin":650,"end":654},"obj":"http://www.ebi.ac.uk/efo/EFO_0000934"},{"id":"T15","span":{"begin":699,"end":702},"obj":"http://purl.obolibrary.org/obo/CLO_0051582"},{"id":"T16","span":{"begin":810,"end":813},"obj":"http://purl.obolibrary.org/obo/CLO_0051582"},{"id":"T17","span":{"begin":931,"end":936},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},{"id":"T18","span":{"begin":937,"end":951},"obj":"http://purl.obolibrary.org/obo/UBERON_0002066"},{"id":"T19","span":{"begin":937,"end":951},"obj":"http://www.ebi.ac.uk/efo/EFO_0001940"},{"id":"T20","span":{"begin":952,"end":969},"obj":"http://purl.obolibrary.org/obo/CL_0000115"},{"id":"T21","span":{"begin":971,"end":977},"obj":"http://purl.obolibrary.org/obo/CLO_0004307"},{"id":"T22","span":{"begin":983,"end":988},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},{"id":"T23","span":{"begin":989,"end":1005},"obj":"http://www.ebi.ac.uk/efo/EFO_0000927"},{"id":"T24","span":{"begin":1006,"end":1009},"obj":"http://purl.obolibrary.org/obo/CLO_0001230"},{"id":"T25","span":{"begin":1006,"end":1009},"obj":"http://purl.obolibrary.org/obo/CLO_0037237"},{"id":"T26","span":{"begin":1006,"end":1009},"obj":"http://purl.obolibrary.org/obo/CLO_0050903"},{"id":"T27","span":{"begin":1006,"end":1009},"obj":"http://purl.obolibrary.org/obo/CLO_0054249"},{"id":"T28","span":{"begin":1006,"end":1009},"obj":"http://purl.obolibrary.org/obo/CLO_0054250"},{"id":"T29","span":{"begin":1006,"end":1009},"obj":"http://purl.obolibrary.org/obo/CLO_0054251"},{"id":"T30","span":{"begin":1006,"end":1009},"obj":"http://purl.obolibrary.org/obo/CLO_0054252"},{"id":"T31","span":{"begin":1020,"end":1025},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T32","span":{"begin":1066,"end":1076},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T33","span":{"begin":1174,"end":1175},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T34","span":{"begin":1383,"end":1384},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T35","span":{"begin":1436,"end":1441},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T36","span":{"begin":1462,"end":1463},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T37","span":{"begin":1658,"end":1661},"obj":"http://www.ebi.ac.uk/efo/EFO_0001410"},{"id":"T38","span":{"begin":1932,"end":1942},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T39","span":{"begin":1964,"end":1974},"obj":"http://purl.obolibrary.org/obo/SO_0000418"}],"text":"2.1 Metformin-AMPK-ACE2-SARS-CoV-2\nThe juggernaut virus, SARS-CoV-2, that has led to the deaths of over 1.7 lakh people across the world uses angiotensin-converting enzyme 2 (ACE2) as its receptor. It enters the human body through interaction between its spike proteins (S1) and the N-terminal region of ACE2 [4], [5]. The receptor binding domain (RBD) of the virus binds with the protease domain (PD) of the ACE2 receptor and forms an RBD-PD complex [4].\nAcute Respiratory Distress Syndrome (ARDS) is one of the commonest complications developing in patients with COVID-19 [6]. There have been animal studies that have implicated ACE2 in the acute lung injury (ALI) caused due to SARS-CoV [4]. It has been hypothesized that ACE2 causes ALI by bringing about autophagy through the AMPK/mTOR pathway [7]. AMPK has been shown to increase the expression of ACE2 as well as to increase its stability by phosphorylating ACE2 Ser680 in human umbilical vein endothelial cells (HUVECs) and human embryonic kidney 293 (HEK293T) cells [8].\nSince metformin works through AMPK activation, which leads to phosphorylation of ACE2 [8], we can consider that theoretically this addition of a phosphate group (PO4 −3) would bring about conformational and functional changes in the ACE2 receptor [9]. This could lead to decreased binding with SARS-CoV-2 RBD due to steric hindrance by the addition of a large sized PO4 −3 molecule.\nNonetheless, once the virus is inside, there is a downregulation of ACE2 receptors. This in turn leads to an imbalance in the renin-angiotensin-aldosterone system (RAS) promoting the deleterious effects of its pro-inflammatory and pro-fibrotic arm, further giving rise to the lethal cardio-pulmonary complications [10]. By upregulating ACE2, the imbalance in RAS could be averted. Hence, metformin would not only prevent the entry of SARS-CoV-2 as described above, but also prevent the detrimental sequelae by causing activation of ACE2 through AMPK-signalling."}

{"project":"LitCovid-PD-CHEBI","denotations":[{"id":"T22","span":{"begin":5,"end":14},"obj":"Chemical"},{"id":"T23","span":{"begin":143,"end":154},"obj":"Chemical"},{"id":"T24","span":{"begin":262,"end":270},"obj":"Chemical"},{"id":"T25","span":{"begin":399,"end":401},"obj":"Chemical"},{"id":"T26","span":{"begin":441,"end":443},"obj":"Chemical"},{"id":"T27","span":{"begin":1037,"end":1046},"obj":"Chemical"},{"id":"T28","span":{"begin":1176,"end":1191},"obj":"Chemical"},{"id":"T30","span":{"begin":1176,"end":1185},"obj":"Chemical"},{"id":"T34","span":{"begin":1186,"end":1191},"obj":"Chemical"},{"id":"T35","span":{"begin":1404,"end":1412},"obj":"Chemical"},{"id":"T36","span":{"begin":1546,"end":1557},"obj":"Chemical"},{"id":"T37","span":{"begin":1558,"end":1569},"obj":"Chemical"},{"id":"T39","span":{"begin":1578,"end":1581},"obj":"Chemical"},{"id":"T40","span":{"begin":1773,"end":1776},"obj":"Chemical"},{"id":"T41","span":{"begin":1802,"end":1811},"obj":"Chemical"}],"attributes":[{"id":"A22","pred":"chebi_id","subj":"T22","obj":"http://purl.obolibrary.org/obo/CHEBI_6801"},{"id":"A23","pred":"chebi_id","subj":"T23","obj":"http://purl.obolibrary.org/obo/CHEBI_48433"},{"id":"A24","pred":"chebi_id","subj":"T24","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A25","pred":"chebi_id","subj":"T25","obj":"http://purl.obolibrary.org/obo/CHEBI_74756"},{"id":"A26","pred":"chebi_id","subj":"T26","obj":"http://purl.obolibrary.org/obo/CHEBI_74756"},{"id":"A27","pred":"chebi_id","subj":"T27","obj":"http://purl.obolibrary.org/obo/CHEBI_6801"},{"id":"A28","pred":"chebi_id","subj":"T28","obj":"http://purl.obolibrary.org/obo/CHEBI_32958"},{"id":"A29","pred":"chebi_id","subj":"T28","obj":"http://purl.obolibrary.org/obo/CHEBI_68546"},{"id":"A30","pred":"chebi_id","subj":"T30","obj":"http://purl.obolibrary.org/obo/CHEBI_18367"},{"id":"A31","pred":"chebi_id","subj":"T30","obj":"http://purl.obolibrary.org/obo/CHEBI_26020"},{"id":"A32","pred":"chebi_id","subj":"T30","obj":"http://purl.obolibrary.org/obo/CHEBI_35780"},{"id":"A33","pred":"chebi_id","subj":"T30","obj":"http://purl.obolibrary.org/obo/CHEBI_43474"},{"id":"A34","pred":"chebi_id","subj":"T34","obj":"http://purl.obolibrary.org/obo/CHEBI_24433"},{"id":"A35","pred":"chebi_id","subj":"T35","obj":"http://purl.obolibrary.org/obo/CHEBI_25367"},{"id":"A36","pred":"chebi_id","subj":"T36","obj":"http://purl.obolibrary.org/obo/CHEBI_48433"},{"id":"A37","pred":"chebi_id","subj":"T37","obj":"http://purl.obolibrary.org/obo/CHEBI_27584"},{"id":"A38","pred":"chebi_id","subj":"T37","obj":"http://purl.obolibrary.org/obo/CHEBI_30834"},{"id":"A39","pred":"chebi_id","subj":"T39","obj":"http://purl.obolibrary.org/obo/CHEBI_63620"},{"id":"A40","pred":"chebi_id","subj":"T40","obj":"http://purl.obolibrary.org/obo/CHEBI_63620"},{"id":"A41","pred":"chebi_id","subj":"T41","obj":"http://purl.obolibrary.org/obo/CHEBI_6801"}],"text":"2.1 Metformin-AMPK-ACE2-SARS-CoV-2\nThe juggernaut virus, SARS-CoV-2, that has led to the deaths of over 1.7 lakh people across the world uses angiotensin-converting enzyme 2 (ACE2) as its receptor. It enters the human body through interaction between its spike proteins (S1) and the N-terminal region of ACE2 [4], [5]. The receptor binding domain (RBD) of the virus binds with the protease domain (PD) of the ACE2 receptor and forms an RBD-PD complex [4].\nAcute Respiratory Distress Syndrome (ARDS) is one of the commonest complications developing in patients with COVID-19 [6]. There have been animal studies that have implicated ACE2 in the acute lung injury (ALI) caused due to SARS-CoV [4]. It has been hypothesized that ACE2 causes ALI by bringing about autophagy through the AMPK/mTOR pathway [7]. AMPK has been shown to increase the expression of ACE2 as well as to increase its stability by phosphorylating ACE2 Ser680 in human umbilical vein endothelial cells (HUVECs) and human embryonic kidney 293 (HEK293T) cells [8].\nSince metformin works through AMPK activation, which leads to phosphorylation of ACE2 [8], we can consider that theoretically this addition of a phosphate group (PO4 −3) would bring about conformational and functional changes in the ACE2 receptor [9]. This could lead to decreased binding with SARS-CoV-2 RBD due to steric hindrance by the addition of a large sized PO4 −3 molecule.\nNonetheless, once the virus is inside, there is a downregulation of ACE2 receptors. This in turn leads to an imbalance in the renin-angiotensin-aldosterone system (RAS) promoting the deleterious effects of its pro-inflammatory and pro-fibrotic arm, further giving rise to the lethal cardio-pulmonary complications [10]. By upregulating ACE2, the imbalance in RAS could be averted. Hence, metformin would not only prevent the entry of SARS-CoV-2 as described above, but also prevent the detrimental sequelae by causing activation of ACE2 through AMPK-signalling."}

{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T7","span":{"begin":15,"end":19},"obj":"http://purl.obolibrary.org/obo/GO_0050405"},{"id":"T8","span":{"begin":15,"end":19},"obj":"http://purl.obolibrary.org/obo/GO_0047322"},{"id":"T9","span":{"begin":15,"end":19},"obj":"http://purl.obolibrary.org/obo/GO_0004691"},{"id":"T10","span":{"begin":760,"end":769},"obj":"http://purl.obolibrary.org/obo/GO_0016236"},{"id":"T11","span":{"begin":760,"end":769},"obj":"http://purl.obolibrary.org/obo/GO_0006914"},{"id":"T12","span":{"begin":782,"end":786},"obj":"http://purl.obolibrary.org/obo/GO_0050405"},{"id":"T13","span":{"begin":782,"end":786},"obj":"http://purl.obolibrary.org/obo/GO_0047322"},{"id":"T14","span":{"begin":782,"end":786},"obj":"http://purl.obolibrary.org/obo/GO_0004691"},{"id":"T15","span":{"begin":805,"end":809},"obj":"http://purl.obolibrary.org/obo/GO_0050405"},{"id":"T16","span":{"begin":805,"end":809},"obj":"http://purl.obolibrary.org/obo/GO_0047322"},{"id":"T17","span":{"begin":805,"end":809},"obj":"http://purl.obolibrary.org/obo/GO_0004691"},{"id":"T18","span":{"begin":900,"end":915},"obj":"http://purl.obolibrary.org/obo/GO_0016310"},{"id":"T19","span":{"begin":1061,"end":1065},"obj":"http://purl.obolibrary.org/obo/GO_0050405"},{"id":"T20","span":{"begin":1061,"end":1065},"obj":"http://purl.obolibrary.org/obo/GO_0047322"},{"id":"T21","span":{"begin":1061,"end":1065},"obj":"http://purl.obolibrary.org/obo/GO_0004691"},{"id":"T22","span":{"begin":1093,"end":1108},"obj":"http://purl.obolibrary.org/obo/GO_0016310"},{"id":"T23","span":{"begin":1959,"end":1963},"obj":"http://purl.obolibrary.org/obo/GO_0050405"},{"id":"T24","span":{"begin":1959,"end":1963},"obj":"http://purl.obolibrary.org/obo/GO_0047322"},{"id":"T25","span":{"begin":1959,"end":1963},"obj":"http://purl.obolibrary.org/obo/GO_0004691"},{"id":"T26","span":{"begin":1964,"end":1974},"obj":"http://purl.obolibrary.org/obo/GO_0023052"}],"text":"2.1 Metformin-AMPK-ACE2-SARS-CoV-2\nThe juggernaut virus, SARS-CoV-2, that has led to the deaths of over 1.7 lakh people across the world uses angiotensin-converting enzyme 2 (ACE2) as its receptor. It enters the human body through interaction between its spike proteins (S1) and the N-terminal region of ACE2 [4], [5]. The receptor binding domain (RBD) of the virus binds with the protease domain (PD) of the ACE2 receptor and forms an RBD-PD complex [4].\nAcute Respiratory Distress Syndrome (ARDS) is one of the commonest complications developing in patients with COVID-19 [6]. There have been animal studies that have implicated ACE2 in the acute lung injury (ALI) caused due to SARS-CoV [4]. It has been hypothesized that ACE2 causes ALI by bringing about autophagy through the AMPK/mTOR pathway [7]. AMPK has been shown to increase the expression of ACE2 as well as to increase its stability by phosphorylating ACE2 Ser680 in human umbilical vein endothelial cells (HUVECs) and human embryonic kidney 293 (HEK293T) cells [8].\nSince metformin works through AMPK activation, which leads to phosphorylation of ACE2 [8], we can consider that theoretically this addition of a phosphate group (PO4 −3) would bring about conformational and functional changes in the ACE2 receptor [9]. This could lead to decreased binding with SARS-CoV-2 RBD due to steric hindrance by the addition of a large sized PO4 −3 molecule.\nNonetheless, once the virus is inside, there is a downregulation of ACE2 receptors. This in turn leads to an imbalance in the renin-angiotensin-aldosterone system (RAS) promoting the deleterious effects of its pro-inflammatory and pro-fibrotic arm, further giving rise to the lethal cardio-pulmonary complications [10]. By upregulating ACE2, the imbalance in RAS could be averted. Hence, metformin would not only prevent the entry of SARS-CoV-2 as described above, but also prevent the detrimental sequelae by causing activation of ACE2 through AMPK-signalling."}

{"project":"LitCovid-sentences","denotations":[{"id":"T12","span":{"begin":0,"end":35},"obj":"Sentence"},{"id":"T13","span":{"begin":36,"end":198},"obj":"Sentence"},{"id":"T14","span":{"begin":199,"end":319},"obj":"Sentence"},{"id":"T15","span":{"begin":320,"end":456},"obj":"Sentence"},{"id":"T16","span":{"begin":457,"end":579},"obj":"Sentence"},{"id":"T17","span":{"begin":580,"end":695},"obj":"Sentence"},{"id":"T18","span":{"begin":696,"end":804},"obj":"Sentence"},{"id":"T19","span":{"begin":805,"end":1030},"obj":"Sentence"},{"id":"T20","span":{"begin":1031,"end":1282},"obj":"Sentence"},{"id":"T21","span":{"begin":1283,"end":1413},"obj":"Sentence"},{"id":"T22","span":{"begin":1414,"end":1497},"obj":"Sentence"},{"id":"T23","span":{"begin":1498,"end":1733},"obj":"Sentence"},{"id":"T24","span":{"begin":1734,"end":1794},"obj":"Sentence"},{"id":"T25","span":{"begin":1795,"end":1975},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"2.1 Metformin-AMPK-ACE2-SARS-CoV-2\nThe juggernaut virus, SARS-CoV-2, that has led to the deaths of over 1.7 lakh people across the world uses angiotensin-converting enzyme 2 (ACE2) as its receptor. It enters the human body through interaction between its spike proteins (S1) and the N-terminal region of ACE2 [4], [5]. The receptor binding domain (RBD) of the virus binds with the protease domain (PD) of the ACE2 receptor and forms an RBD-PD complex [4].\nAcute Respiratory Distress Syndrome (ARDS) is one of the commonest complications developing in patients with COVID-19 [6]. There have been animal studies that have implicated ACE2 in the acute lung injury (ALI) caused due to SARS-CoV [4]. It has been hypothesized that ACE2 causes ALI by bringing about autophagy through the AMPK/mTOR pathway [7]. AMPK has been shown to increase the expression of ACE2 as well as to increase its stability by phosphorylating ACE2 Ser680 in human umbilical vein endothelial cells (HUVECs) and human embryonic kidney 293 (HEK293T) cells [8].\nSince metformin works through AMPK activation, which leads to phosphorylation of ACE2 [8], we can consider that theoretically this addition of a phosphate group (PO4 −3) would bring about conformational and functional changes in the ACE2 receptor [9]. This could lead to decreased binding with SARS-CoV-2 RBD due to steric hindrance by the addition of a large sized PO4 −3 molecule.\nNonetheless, once the virus is inside, there is a downregulation of ACE2 receptors. This in turn leads to an imbalance in the renin-angiotensin-aldosterone system (RAS) promoting the deleterious effects of its pro-inflammatory and pro-fibrotic arm, further giving rise to the lethal cardio-pulmonary complications [10]. By upregulating ACE2, the imbalance in RAS could be averted. Hence, metformin would not only prevent the entry of SARS-CoV-2 as described above, but also prevent the detrimental sequelae by causing activation of ACE2 through AMPK-signalling."}

{"project":"LitCovid-PD-HP","denotations":[{"id":"T1","span":{"begin":463,"end":483},"obj":"Phenotype"},{"id":"T2","span":{"begin":644,"end":661},"obj":"Phenotype"},{"id":"T3","span":{"begin":663,"end":666},"obj":"Phenotype"},{"id":"T4","span":{"begin":738,"end":741},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/HP_0002098"},{"id":"A2","pred":"hp_id","subj":"T2","obj":"http://www.orpha.net/ORDO/Orphanet_178320"},{"id":"A3","pred":"hp_id","subj":"T3","obj":"http://www.orpha.net/ORDO/Orphanet_178320"},{"id":"A4","pred":"hp_id","subj":"T4","obj":"http://www.orpha.net/ORDO/Orphanet_178320"}],"text":"2.1 Metformin-AMPK-ACE2-SARS-CoV-2\nThe juggernaut virus, SARS-CoV-2, that has led to the deaths of over 1.7 lakh people across the world uses angiotensin-converting enzyme 2 (ACE2) as its receptor. It enters the human body through interaction between its spike proteins (S1) and the N-terminal region of ACE2 [4], [5]. The receptor binding domain (RBD) of the virus binds with the protease domain (PD) of the ACE2 receptor and forms an RBD-PD complex [4].\nAcute Respiratory Distress Syndrome (ARDS) is one of the commonest complications developing in patients with COVID-19 [6]. There have been animal studies that have implicated ACE2 in the acute lung injury (ALI) caused due to SARS-CoV [4]. It has been hypothesized that ACE2 causes ALI by bringing about autophagy through the AMPK/mTOR pathway [7]. AMPK has been shown to increase the expression of ACE2 as well as to increase its stability by phosphorylating ACE2 Ser680 in human umbilical vein endothelial cells (HUVECs) and human embryonic kidney 293 (HEK293T) cells [8].\nSince metformin works through AMPK activation, which leads to phosphorylation of ACE2 [8], we can consider that theoretically this addition of a phosphate group (PO4 −3) would bring about conformational and functional changes in the ACE2 receptor [9]. This could lead to decreased binding with SARS-CoV-2 RBD due to steric hindrance by the addition of a large sized PO4 −3 molecule.\nNonetheless, once the virus is inside, there is a downregulation of ACE2 receptors. This in turn leads to an imbalance in the renin-angiotensin-aldosterone system (RAS) promoting the deleterious effects of its pro-inflammatory and pro-fibrotic arm, further giving rise to the lethal cardio-pulmonary complications [10]. By upregulating ACE2, the imbalance in RAS could be averted. Hence, metformin would not only prevent the entry of SARS-CoV-2 as described above, but also prevent the detrimental sequelae by causing activation of ACE2 through AMPK-signalling."}

{"project":"2_test","denotations":[{"id":"32360697-32142651-25244884","span":{"begin":316,"end":317},"obj":"32142651"},{"id":"32360697-31986264-25244885","span":{"begin":576,"end":577},"obj":"31986264"},{"id":"32360697-31356776-25244886","span":{"begin":801,"end":802},"obj":"31356776"}],"text":"2.1 Metformin-AMPK-ACE2-SARS-CoV-2\nThe juggernaut virus, SARS-CoV-2, that has led to the deaths of over 1.7 lakh people across the world uses angiotensin-converting enzyme 2 (ACE2) as its receptor. It enters the human body through interaction between its spike proteins (S1) and the N-terminal region of ACE2 [4], [5]. The receptor binding domain (RBD) of the virus binds with the protease domain (PD) of the ACE2 receptor and forms an RBD-PD complex [4].\nAcute Respiratory Distress Syndrome (ARDS) is one of the commonest complications developing in patients with COVID-19 [6]. There have been animal studies that have implicated ACE2 in the acute lung injury (ALI) caused due to SARS-CoV [4]. It has been hypothesized that ACE2 causes ALI by bringing about autophagy through the AMPK/mTOR pathway [7]. AMPK has been shown to increase the expression of ACE2 as well as to increase its stability by phosphorylating ACE2 Ser680 in human umbilical vein endothelial cells (HUVECs) and human embryonic kidney 293 (HEK293T) cells [8].\nSince metformin works through AMPK activation, which leads to phosphorylation of ACE2 [8], we can consider that theoretically this addition of a phosphate group (PO4 −3) would bring about conformational and functional changes in the ACE2 receptor [9]. This could lead to decreased binding with SARS-CoV-2 RBD due to steric hindrance by the addition of a large sized PO4 −3 molecule.\nNonetheless, once the virus is inside, there is a downregulation of ACE2 receptors. This in turn leads to an imbalance in the renin-angiotensin-aldosterone system (RAS) promoting the deleterious effects of its pro-inflammatory and pro-fibrotic arm, further giving rise to the lethal cardio-pulmonary complications [10]. By upregulating ACE2, the imbalance in RAS could be averted. Hence, metformin would not only prevent the entry of SARS-CoV-2 as described above, but also prevent the detrimental sequelae by causing activation of ACE2 through AMPK-signalling."}

{"project":"LitCovid-PubTator","denotations":[{"id":"38","span":{"begin":15,"end":19},"obj":"Gene"},{"id":"39","span":{"begin":20,"end":24},"obj":"Gene"},{"id":"50","span":{"begin":143,"end":174},"obj":"Gene"},{"id":"51","span":{"begin":176,"end":180},"obj":"Gene"},{"id":"52","span":{"begin":305,"end":309},"obj":"Gene"},{"id":"53","span":{"begin":410,"end":414},"obj":"Gene"},{"id":"54","span":{"begin":58,"end":68},"obj":"Species"},{"id":"55","span":{"begin":114,"end":120},"obj":"Species"},{"id":"56","span":{"begin":213,"end":218},"obj":"Species"},{"id":"57","span":{"begin":90,"end":96},"obj":"Disease"},{"id":"58","span":{"begin":399,"end":401},"obj":"Disease"},{"id":"59","span":{"begin":441,"end":443},"obj":"Disease"},{"id":"78","span":{"begin":632,"end":636},"obj":"Gene"},{"id":"79","span":{"begin":726,"end":730},"obj":"Gene"},{"id":"80","span":{"begin":782,"end":786},"obj":"Gene"},{"id":"81","span":{"begin":787,"end":791},"obj":"Gene"},{"id":"82","span":{"begin":805,"end":809},"obj":"Gene"},{"id":"83","span":{"begin":855,"end":859},"obj":"Gene"},{"id":"84","span":{"begin":916,"end":920},"obj":"Gene"},{"id":"85","span":{"begin":552,"end":560},"obj":"Species"},{"id":"86","span":{"begin":682,"end":690},"obj":"Species"},{"id":"87","span":{"begin":931,"end":936},"obj":"Species"},{"id":"88","span":{"begin":983,"end":988},"obj":"Species"},{"id":"89","span":{"begin":921,"end":927},"obj":"Chemical"},{"id":"90","span":{"begin":457,"end":492},"obj":"Disease"},{"id":"91","span":{"begin":494,"end":498},"obj":"Disease"},{"id":"92","span":{"begin":566,"end":574},"obj":"Disease"},{"id":"93","span":{"begin":644,"end":661},"obj":"Disease"},{"id":"94","span":{"begin":989,"end":1005},"obj":"Disease"},{"id":"95","span":{"begin":1006,"end":1019},"obj":"CellLine"},{"id":"103","span":{"begin":1061,"end":1065},"obj":"Gene"},{"id":"104","span":{"begin":1112,"end":1116},"obj":"Gene"},{"id":"105","span":{"begin":1264,"end":1268},"obj":"Gene"},{"id":"106","span":{"begin":1325,"end":1335},"obj":"Species"},{"id":"107","span":{"begin":1037,"end":1046},"obj":"Chemical"},{"id":"108","span":{"begin":1176,"end":1185},"obj":"Chemical"},{"id":"109","span":{"begin":1397,"end":1403},"obj":"Chemical"},{"id":"117","span":{"begin":1482,"end":1486},"obj":"Gene"},{"id":"118","span":{"begin":1750,"end":1754},"obj":"Gene"},{"id":"119","span":{"begin":1946,"end":1950},"obj":"Gene"},{"id":"120","span":{"begin":1959,"end":1963},"obj":"Gene"},{"id":"121","span":{"begin":1848,"end":1858},"obj":"Species"},{"id":"122","span":{"begin":1558,"end":1569},"obj":"Chemical"},{"id":"123","span":{"begin":1802,"end":1811},"obj":"Chemical"}],"attributes":[{"id":"A38","pred":"tao:has_database_id","subj":"38","obj":"Gene:5563"},{"id":"A39","pred":"tao:has_database_id","subj":"39","obj":"Gene:59272"},{"id":"A50","pred":"tao:has_database_id","subj":"50","obj":"Gene:59272"},{"id":"A51","pred":"tao:has_database_id","subj":"51","obj":"Gene:59272"},{"id":"A52","pred":"tao:has_database_id","subj":"52","obj":"Gene:59272"},{"id":"A53","pred":"tao:has_database_id","subj":"53","obj":"Gene:59272"},{"id":"A54","pred":"tao:has_database_id","subj":"54","obj":"Tax:2697049"},{"id":"A55","pred":"tao:has_database_id","subj":"55","obj":"Tax:9606"},{"id":"A56","pred":"tao:has_database_id","subj":"56","obj":"Tax:9606"},{"id":"A57","pred":"tao:has_database_id","subj":"57","obj":"MESH:D003643"},{"id":"A58","pred":"tao:has_database_id","subj":"58","obj":"MESH:D010300"},{"id":"A59","pred":"tao:has_database_id","subj":"59","obj":"MESH:D010300"},{"id":"A78","pred":"tao:has_database_id","subj":"78","obj":"Gene:59272"},{"id":"A79","pred":"tao:has_database_id","subj":"79","obj":"Gene:59272"},{"id":"A80","pred":"tao:has_database_id","subj":"80","obj":"Gene:5563"},{"id":"A81","pred":"tao:has_database_id","subj":"81","obj":"Gene:2475"},{"id":"A82","pred":"tao:has_database_id","subj":"82","obj":"Gene:5563"},{"id":"A83","pred":"tao:has_database_id","subj":"83","obj":"Gene:59272"},{"id":"A84","pred":"tao:has_database_id","subj":"84","obj":"Gene:59272"},{"id":"A85","pred":"tao:has_database_id","subj":"85","obj":"Tax:9606"},{"id":"A86","pred":"tao:has_database_id","subj":"86","obj":"Tax:694009"},{"id":"A87","pred":"tao:has_database_id","subj":"87","obj":"Tax:9606"},{"id":"A88","pred":"tao:has_database_id","subj":"88","obj":"Tax:9606"},{"id":"A90","pred":"tao:has_database_id","subj":"90","obj":"MESH:D012128"},{"id":"A91","pred":"tao:has_database_id","subj":"91","obj":"MESH:D012128"},{"id":"A92","pred":"tao:has_database_id","subj":"92","obj":"MESH:C000657245"},{"id":"A93","pred":"tao:has_database_id","subj":"93","obj":"MESH:D055371"},{"id":"A94","pred":"tao:has_database_id","subj":"94","obj":"MESH:D007674"},{"id":"A95","pred":"tao:has_database_id","subj":"95","obj":"CVCL:0063"},{"id":"A103","pred":"tao:has_database_id","subj":"103","obj":"Gene:5563"},{"id":"A104","pred":"tao:has_database_id","subj":"104","obj":"Gene:59272"},{"id":"A105","pred":"tao:has_database_id","subj":"105","obj":"Gene:59272"},{"id":"A106","pred":"tao:has_database_id","subj":"106","obj":"Tax:2697049"},{"id":"A107","pred":"tao:has_database_id","subj":"107","obj":"MESH:D008687"},{"id":"A108","pred":"tao:has_database_id","subj":"108","obj":"MESH:D010710"},{"id":"A117","pred":"tao:has_database_id","subj":"117","obj":"Gene:59272"},{"id":"A118","pred":"tao:has_database_id","subj":"118","obj":"Gene:59272"},{"id":"A119","pred":"tao:has_database_id","subj":"119","obj":"Gene:59272"},{"id":"A120","pred":"tao:has_database_id","subj":"120","obj":"Gene:5563"},{"id":"A121","pred":"tao:has_database_id","subj":"121","obj":"Tax:2697049"},{"id":"A122","pred":"tao:has_database_id","subj":"122","obj":"MESH:D000450"},{"id":"A123","pred":"tao:has_database_id","subj":"123","obj":"MESH:D008687"}],"namespaces":[{"prefix":"Tax","uri":"https://www.ncbi.nlm.nih.gov/taxonomy/"},{"prefix":"MESH","uri":"https://id.nlm.nih.gov/mesh/"},{"prefix":"Gene","uri":"https://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"CVCL","uri":"https://web.expasy.org/cellosaurus/CVCL_"}],"text":"2.1 Metformin-AMPK-ACE2-SARS-CoV-2\nThe juggernaut virus, SARS-CoV-2, that has led to the deaths of over 1.7 lakh people across the world uses angiotensin-converting enzyme 2 (ACE2) as its receptor. It enters the human body through interaction between its spike proteins (S1) and the N-terminal region of ACE2 [4], [5]. The receptor binding domain (RBD) of the virus binds with the protease domain (PD) of the ACE2 receptor and forms an RBD-PD complex [4].\nAcute Respiratory Distress Syndrome (ARDS) is one of the commonest complications developing in patients with COVID-19 [6]. There have been animal studies that have implicated ACE2 in the acute lung injury (ALI) caused due to SARS-CoV [4]. It has been hypothesized that ACE2 causes ALI by bringing about autophagy through the AMPK/mTOR pathway [7]. AMPK has been shown to increase the expression of ACE2 as well as to increase its stability by phosphorylating ACE2 Ser680 in human umbilical vein endothelial cells (HUVECs) and human embryonic kidney 293 (HEK293T) cells [8].\nSince metformin works through AMPK activation, which leads to phosphorylation of ACE2 [8], we can consider that theoretically this addition of a phosphate group (PO4 −3) would bring about conformational and functional changes in the ACE2 receptor [9]. This could lead to decreased binding with SARS-CoV-2 RBD due to steric hindrance by the addition of a large sized PO4 −3 molecule.\nNonetheless, once the virus is inside, there is a downregulation of ACE2 receptors. This in turn leads to an imbalance in the renin-angiotensin-aldosterone system (RAS) promoting the deleterious effects of its pro-inflammatory and pro-fibrotic arm, further giving rise to the lethal cardio-pulmonary complications [10]. By upregulating ACE2, the imbalance in RAS could be averted. Hence, metformin would not only prevent the entry of SARS-CoV-2 as described above, but also prevent the detrimental sequelae by causing activation of ACE2 through AMPK-signalling."}