LitCovid-sentences  

PubMed:32418532 JSONTXT 27 Projects

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Id Subject Object Predicate Lexical cue
T1 0-127 Sentence denotes Counter-regulatory 'Renin-Angiotensin' System-based Candidate Drugs to Treat COVID-19 Diseases in SARS-CoV-2-infected patients.
T2 128-424 Sentence denotes SARS-CoV-2 / COVID-19 and the 'Renin-Angiotensin' System The ubiquitous 'Renin-Angiotensin' system (RAS), also referred to as 'Renin-Angiotensin-Aldosterone' system, plays a crucial physiological role in humans as being a key regulator of renal, cardiovascular and innate immune functions [1, 2].
T3 425-567 Sentence denotes It appears to work in tandem with vitamin D, a secosteroid pro-hormone which reportedly acts as a negative regulatory factor of the RAS [3-6].
T4 568-986 Sentence denotes A dysfunction (e.g. over-reactivity) of RAS, together with hypovitaminosis D, is likely associated with some of the various renal, cardiac, vascular and immune outcomes that might be observed in COVID-19 patients, including the cytokine storm (i.e. unopposed hyperactive immune reaction generating both pro-inflammatory and anti-inflammatory cytokines) and consequent lethal acute respiratory distress syndrome [1, 7].
T5 987-1425 Sentence denotes Recently, SARS-CoV-2 [8, 9], the causative agent of COVID-19, has been described to interfere with the RAS [2] by interacting -via its spike (S) glycoprotein- with the metallopeptidase Angiotensin-Converting Enzyme 2 (ACE2) receptor [9, 10] that is expressed at the surface of epithelial cells from blood vessels, lung, kidney (renal tubules), intestine, and heart, as well as on cerebral neurons and immune monocytes/macrophages [11-13].
T6 1426-1768 Sentence denotes The main SARS-CoV-2-related COVID-19 symptoms/diseases reported hitherto are hypertension, atherosclerosis, thrombosis (coagulopathy), diarrhea, glaucoma, anosmia, ageusia, skin lesions (dermatitis), autoimmune inflammation of the central nervous system, and damages to various organs such as the lung, heart, kidney, and testicle [1, 2, 14].
T7 1769-1882 Sentence denotes All these diffuse COVID-19 disorders are likely linked to an over-reaction of RAS in SARS-CoV-2-infected persons.
T8 1883-1957 Sentence denotes Such a RAS imbalance would be also favored by hypovitaminosis D [2-7, 11].
T9 1958-2130 Sentence denotes Since RAS appears to be central in COVID-19 symptoms/diseases, selective targeting of key component(s) of this system might be appropriate to treat RAS-dependent disorders.
T10 2131-2332 Sentence denotes COVID-19 Disorders: 'Renin-Angiotensin' System (RAS) & Counter-regulatory RAS In the RAS pathway [1, 15], Renin (kidney) cleaves Angiotensinogen (liver) to give Angiotensin I (i.e. peptide DRVYIHPFHL).
T11 2333-2528 Sentence denotes The latter is cleaved by the Angiotensin-Converting Enzyme (ACE) to produce Angiotensin II (i.e. peptide DRVYIHPF), which is the substrate of ACE2 (SARS-CoV-2 receptor) and key player of the RAS.
T12 2529-2787 Sentence denotes The cellular targets of Angiotensin II are the vasoconstrictor type 1 (AT1R) and vasodilatator type 2 (AT2R) Angiotensin II receptors (AT1R is expressed at the surface of monocytes/macrophages and T-cells indicating that RAS acts on innate immunity in host).
T13 2788-2934 Sentence denotes When cleaved by ACE2, Angiotensin II gives Angiotensin 1-7 (i.e. peptide DRVYIHP), targeting the vasodilatator proto-oncogene Mas receptor (MasR).
T14 2935-3045 Sentence denotes Angiotensin 1-7 can be further transformed to Alamandine (i.e. peptide ARVYIHP) by an aspartate decarboxylase.
T15 3046-3200 Sentence denotes Alamandine would bind to the vasodilatator Mas-related G protein-coupled receptor member D (MRGD) thus promoting most of the Angiotensin 1-7-like effects.
T16 3201-3345 Sentence denotes Angiotensin II can produce Angiotensin A (i.e. peptide ARVYIHPF) via an aspartate decarboxylase, and Alamandine via an additional ACE2 cleavage.
T17 3346-3450 Sentence denotes ACE2 can also cleave Angiotensin I to form Angiotensin 1-9 (i.e. peptide DRVYIHPFH), which targets AT2R.
T18 3451-3650 Sentence denotes In the RAS pathway were finally evidenced the related Angiotensin III (i.e. peptide RVYIHPF) and Angiotensin IV (i.e. peptide VYIHPF) variants targeting the AT1R and vasodilatator AT4R, respectively.
T19 3651-3850 Sentence denotes From the known molecular functioning of the RAS, Angiotensins I and II (aside Angiotensin III) are playing central roles in the activity of RAS and associated pathologies, including COVID-19 [2, 10].
T20 3851-4140 Sentence denotes Interestingly, it appears that a 'counter-regulatory' RAS does exist to modulate system homeostasis; it relies on Angiotensin 1-7, Angiotensin 1-9, Alamandine, Angiotensin A, and Angiotensin IV, which are targeting the MasR, AT2R, MRGD, ACE2 and AT4R vasodilatator receptors, respectively.
T21 4141-4287 Sentence denotes These peptides were found to exhibit cardioprotective, vasoactive (anti-hypertensive), anti-hypertrophic and/or anti-inflammatory potentials [15].
T22 4288-4468 Sentence denotes Such naturally-produced molecules of the RAS are expected to counteract the SARS-CoV-2-induced over-activation of RAS and reverse, to some extent, the associated COVID-19 diseases.
T23 4469-4616 Sentence denotes CONCLUDING REMARKS A recent report suggests that RAS inhibitors may act on the severity of viral infection and mortality of COVID-19 patients [14].
T24 4617-4706 Sentence denotes Whether or not RAS blockers would be beneficial to COVID-19 cases is still controversial.
T25 4707-4839 Sentence denotes The RAS inhibitors likely prevent the cytokine storm as RAS is reported to control the release of pro-inflammatory cytokines [1, 7].
T26 4840-5001 Sentence denotes It appears that COVID-19 disorders of SARS-CoV-2-infected humans depend on the RAS over-reacted by the (ACE2-dependent) viral infection and vitamin D deficiency.
T27 5002-5117 Sentence denotes The track for a possible COVID-19 treatment would be to target RAS using specific candidate chemotherapeutic drugs.
T28 5118-5301 Sentence denotes The proposed molecules are (so far) ACE inhibitors (to prevent the production of Angiotensin II from Angiotensin I), and blockers/antagonists of AT1R such as Losartan and derivatives.
T29 5302-5469 Sentence denotes Recombinant ACE2 (under clinical trials) is also considered as a decoy for the recognition and competitive binding to the spike (S) glycoprotein of SARS-CoV-2 [9, 10].
T30 5470-5684 Sentence denotes We support the use of natural candidate peptide drugs that belong to the 'counter-regulatory' RAS, i.e. Angiotensin 1-7, Angiotensin 1-9, Alamandine, Angiotensin A and/or Angiotensin IV to treat COVID-19 disorders.
T31 5685-5754 Sentence denotes The targeted receptors would thus be MasR, AT2R, MRGD, ACE2 and AT4R.
T32 5755-5826 Sentence denotes The authors wish to thank Bonabes De Rougé MD for fruitful discussions.