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1.
J Phys Chem B ; 126(12): 2353-2360, 2022 Mar 31.
Article in English | MEDLINE | ID: covidwho-1751666

ABSTRACT

Variants of the SARS-CoV-2 virus continue to remain a threat 2 years from the beginning of the pandemic. As more variants arise, and the B.1.1.529 (Omicron) variant threatens to create another wave of infections, a method is needed to predict the binding affinity of the spike protein quickly and accurately with human angiotensin-converting enzyme II (ACE2). We present an accurate and convenient energy minimization/molecular mechanics Poisson-Boltzmann surface area methodology previously used with engineered ACE2 therapeutics to predict the binding affinity of the Omicron variant. Without any additional data from the variants discovered after the publication of our first model, the methodology can accurately predict the binding of the spike/ACE2 variant complexes. From this methodology, we predicted that the Omicron variant spike has a Kd of ∼22.69 nM (which is very close to the experimental Kd of 20.63 nM published during the review process of the current report) and that spike protein of the new "Stealth" Omicron variant (BA.2) will display a Kd of ∼12.9 nM with the wild-type ACE2 protein. This methodology can be used with as-yet discovered variants, allowing for quick determinations regarding the variant's infectivity versus either the wild-type virus or its variants.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Angiotensins , Humans , Membrane Glycoproteins/metabolism , Peptidyl-Dipeptidase A/metabolism , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Viral Envelope Proteins
2.
Adv Exp Med Biol ; 1327: 205-214, 2021.
Article in English | MEDLINE | ID: covidwho-1718516

ABSTRACT

The exaggerated host response to Sars-CoV-2 plays an important role in COVID-19 pathology but provides a therapeutic opportunity until definitive virus targeted therapies and vaccines become available. Given a central role of endothelial dysfunction and systemic inflammation, repurposing ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), statins, and aspirin has been of interest. In this retrospective, single-center study, we evaluated the primary outcomes of mortality and ICU admission in 587 hospitalized patients with documented COVID-19 with or without ACEIs, ARBs, statins, and aspirin. Atorvastatin was associated with reduced mortality, which persisted after adjusting for age, lockdown status, and other medications (OR: 0.18. 95% CI: 0.06-0.49, P = 0.001). ACEIs were also associated with reduced mortality in the crude model (OR: 0.20, CI: 0.06-0.66, P = 0.008), as ACEIs and ARBs were combined as a single group (OR: 0.35, CI: 0.16-0.75, P = 0.007), although ARBs alone did not reach statistical significance. There was no association between any medications and risk of ICU admission. Aspirin only achieved a significant association of reduced mortality in a subgroup of patients with diabetes in the crude model (OR: 0.17, CI: 0.04-0.80, P = 0.02). The reduced mortality observed with atorvastatin is consistent with other literature, and consideration should be given to atorvastatin as a COVID-19 treatment. While there was suggested benefit of ACEIs and ARBs in the present study, other studies are varied and further studies are warranted to recommend employing these medications as a treatment strategy. Nevertheless, this study combined with others continues to give credibility that ACEIs and ARBs are safe to continue in the setting of COVID-19.


Subject(s)
COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Hypertension , Aldosterone , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Angiotensins , Aspirin/therapeutic use , COVID-19/drug therapy , Communicable Disease Control , Hospitals , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Intensive Care Units , Renin , Retrospective Studies , SARS-CoV-2
3.
Mol Pain ; 18: 17448069221080305, 2022.
Article in English | MEDLINE | ID: covidwho-1700706

ABSTRACT

Nervous system manifestations caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of great concern. Neurological symptoms and the neurological effects induced by SARS-CoV-2, such as the loss of various sensory perceptions, indicate direct viral invasion into sensory neurons. Therefore, it is very important to identify the distribution of angiotensin-converting enzyme 2 (ACE2), the receptor of SARS-CoV-2, in human nervous system. However, autofluorescence from lipofuscin obviously impacted immunofluorescence analysis in previous studies. We demonstrated that Sudan Black B (SBB) remarkably reduced the massive lipofuscin-like autofluorescence and the immunofluorescence signal would be sharpened following the exposure compensation. Additionally, we confirmed that ACE2 was expressed in IB4+, CGRP+, and NF200+ sensory subpopulations. The mapping of ACE2 distribution in hDRG would facilitate the understanding of sensory disorder induced by SARS-CoV-2.


Subject(s)
COVID-19 , Peptidyl-Dipeptidase A , Angiotensins , Azo Compounds , Humans , Naphthalenes , Nociceptors , Peptidyl-Dipeptidase A/physiology , SARS-CoV-2
4.
J Chem Inf Model ; 62(3): 656-667, 2022 02 14.
Article in English | MEDLINE | ID: covidwho-1641824

ABSTRACT

The viral entry process of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires heparin and heparan sulfates from the cell surface, functioning as a cofactor for human angiotensin-converting enzyme 2 (ACE2) for recognizing the receptor-binding domain (RBD) of the spike (S) protein on the surface of the virion. In the present study, the binding poses of an oligosaccharide with four repeating units of GlcNS6S-IdoA2S (octa) predicted by Vina-Carb in the RBD binding site were employed in molecular dynamics (MD) simulations to provide atomic details for studying the cofactor mechanism. The molecular model in the MD simulations reproduced the length- and sequence-dependent behavior observed from the microarray experiments and revealed an important planar U-turn shape for HP/HS binding to RBD. The model for octa with this shape in the ACE2-RBD complex enhanced the interactions in the binding interface. The comparisons with the ACE2-RBD complex suggested that the presence of octa in the RBD binding site blocked the movements in a loop region at the distal end of the RBD binding interface and promoted the contacts of this loop region with the ACE2 N-terminus helix. This study shed light on the atomic and dynamic details for HP/HS interacting with RBD and provided insights into their cofactor role in the ACE2-RBD interactions.


Subject(s)
COVID-19 , Heparin , Angiotensins , Binding Sites , Heparitin Sulfate , Humans , Molecular Dynamics Simulation , Protein Binding , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
5.
Am J Rhinol Allergy ; 36(3): 313-322, 2022 May.
Article in English | MEDLINE | ID: covidwho-1605735

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses angiotensin-converting enzyme-2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) as a primary receptor for invasion. Cell entry by the virus requires the co-expression of these molecules in the host cells. OBJECTIVE: We investigated ACE2 and TMPRSS2 expression and localization in paranasal epithelium of eosinophilic chronic rhinosinusitis (ECRS) patients (n = 38), non-ECRS (n = 31), and healthy controls (n = 25). CRS inflammatory patterns are characterized by the type of cytokines; we investigated whether inflammatory endotypes are associated with cell-entry molecules, as this could be linked to susceptibility to SARS-CoV-2 infection. METHODS: The ACE2, TMPRSS2, and other inflammatory cytokine mRNA levels were assessed by quantitative RT-PCR. The localizations of ACE2- and TMPRSS2-positive cells were examined with immunofluorescent double-staining using laser scanning confocal microscopy (LSCM). RESULTS: The non-ECRS patients showed significantly increased ACE2 and TMPRSS2 mRNA expressions compared to the ECRS patients. The CRS patients' ACE2 and TMPRSS2 mRNA levels were positively correlated with IFN-γ (r = 0.3227 and r = 0.3264, respectively) and TNF-α (r = 0.4008, r = 0.3962, respectively). ACE2 and TMPRSS2 were negatively correlated with tissue eosinophils (r = -0.3308, r = -0.3112, respectively), but not with IL-13. ACE2 mRNA levels were positively correlated with TMPRSS2 (r = 0.7478). ACE2 and TMPRSS2 immunoreactivities were localized mainly in the epithelial ciliated cells, as confirmed by co-staining with TMPRSS2 and acetylated α-tubulin, a cilia organelle marker. Using LSCM imaging, we observed higher expressions of these molecules in the non-ECRS patients versus the ECRS patients. CONCLUSION: ECRS patients with type 2 inflammation showed decreased ACE2 and TMPRSS2 expressions in their sinus mucosa. ACE2 and TMPRSS2 regulation seems to be positively related to IFN-γ and TNF-α production in CRS patients; ACE2 and TMPRSS2 were co-expressed in the ciliated epithelium of their paranasal mucosa, implicating the paranasal epithelium as a portal for initial infection and transmission.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19 , Angiotensin-Converting Enzyme 2/genetics , Angiotensins , COVID-19/genetics , Epithelium , Humans , SARS-CoV-2 , Serine Endopeptidases/genetics
6.
Cardiovasc Hematol Disord Drug Targets ; 21(4): 235-242, 2021.
Article in English | MEDLINE | ID: covidwho-1573714

ABSTRACT

AIMS: The study aimed to assess the inhibitory effect of Vitamin C on angiotensin-converting enzyme 2. BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which uses angiotensin-converting enzyme 2 (ACE-II) as the first route to infect human cells. Accordingly, agents with potential inhibition of ACE-II receptors might be effective in the prevention and management of COVID-19. OBJECTIVE: The goal of this work was to assess the possible inhibitory effect of ACE-II on ascorbic acid using an ex vivo approach based on the inhibition of diminazene-induced vasorelaxation. MATERIALS AND METHODS: In the present study, diminazene was used as a known specific inhibitor of ACE-II. Then, the vasorelaxant effect of ascorbic acid on diminazene-induced relaxation was examined using isolated aortic rings. All experiments of this study were evaluated on isolated aortic rings precontracted by epinephrine. RESULTS: The results confirmed that diminazene-induced vasorelaxation in a dose-dependent manner. More interestingly, ascorbic acid inhibited diminazene-induced vasorelaxation in a dose-dependent manner. CONCLUSION: This investigation provides valuable experimental proof of the efficacy of ascorbic acid (Vitamin C) on inhibiting ex vivo vascular angiotensin-converting enzyme II, which is known among the pharmacological targets of anti-COVID-19 drugs.


Subject(s)
Ascorbic Acid , COVID-19 , Angiotensin-Converting Enzyme 2 , Angiotensins , Animals , Ascorbic Acid/pharmacology , Humans , Rats , SARS-CoV-2
7.
Dokl Biochem Biophys ; 502(1): 1-4, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1555645

ABSTRACT

SARS-CoV-2 is a new coronavirus that is the cause of COVID-19 pandemic. To enter the cell, the virus interacts via its surface S protein with angiotensin-converting enzyme 2 (ACE2), the main entry receptor on the cell membrane. Most of protective antibodies, including those induced by vaccinations, target the S protein, preventing its interaction with the ACE2 receptor. We have evaluated an alternative strategy for blocking the S-ACE2 interaction using new antipeptide antibodies to the N-terminus of the ACE2 molecule. These antibodies allow detection of human ACE2 in vitro and ex vivo.


Subject(s)
Angiotensin-Converting Enzyme 2/immunology , COVID-19 , Pandemics , Angiotensins/metabolism , Humans , Pandemics/prevention & control , Protein Binding , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
9.
Biol Sex Differ ; 12(1): 63, 2021 11 22.
Article in English | MEDLINE | ID: covidwho-1528694

ABSTRACT

BACKGROUND: Several biomarkers have been identified to predict the outcome of COVID-19 severity, but few data are available regarding sex differences in their predictive role. Aim of this study was to identify sex-specific biomarkers of severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19. METHODS: Plasma levels of sex hormones (testosterone and 17ß-estradiol), sex-hormone dependent circulating molecules (ACE2 and Angiotensin1-7) and other known biomarkers for COVID-19 severity were measured in male and female COVID-19 patients at admission to hospital. The association of plasma biomarker levels with ARDS severity at admission and with the occurrence of respiratory deterioration during hospitalization was analysed in aggregated and sex disaggregated form. RESULTS: Our data show that some biomarkers could be predictive both for males and female patients and others only for one sex. Angiotensin1-7 plasma levels and neutrophil count predicted the outcome of ARDS only in females, whereas testosterone plasma levels and lymphocytes counts only in males. CONCLUSIONS: Sex is a biological variable affecting the choice of the correct biomarker that might predict worsening of COVID-19 to severe respiratory failure. The definition of sex specific biomarkers can be useful to alert patients to be safely discharged versus those who need respiratory monitoring.


Subject(s)
Biomarkers/blood , COVID-19/complications , Hospitalization , Respiratory Distress Syndrome/complications , Respiratory Distress Syndrome/diagnosis , Respiratory Insufficiency/complications , Respiratory Insufficiency/diagnosis , Sex Characteristics , Adult , Angiotensin-Converting Enzyme 2/blood , Angiotensins/blood , COVID-19/blood , Estradiol/blood , Female , Humans , Male , Middle Aged , Respiratory Distress Syndrome/blood , Respiratory Insufficiency/blood , SARS-CoV-2 , Testosterone/blood
10.
Inflamm Res ; 71(1): 39-56, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1525531

ABSTRACT

The COVID-19 pandemic created a worldwide debilitating health crisis with the entire humanity suffering from the deleterious effects associated with the high infectivity and mortality rates. While significant evidence is currently available online and targets various aspects of the disease, both inflammatory and noninflammatory kidney manifestations secondary to COVID-19 infection are still largely underrepresented. In this review, we summarized current knowledge about COVID-19-related kidney manifestations, their pathologic mechanisms as well as various pharmacotherapies used to treat patients with COVID-19. We also shed light on the effect of these medications on kidney functions that can further enhance renal damage secondary to the illness.


Subject(s)
COVID-19/drug therapy , COVID-19/physiopathology , Kidney Diseases/physiopathology , Kidney/injuries , Acute Kidney Injury/complications , Aldosterone/metabolism , Angiotensins/chemistry , Antibodies, Monoclonal, Humanized/administration & dosage , Autopsy , Biopsy , COVID-19/complications , COVID-19 Vaccines , Dexamethasone/administration & dosage , Enoxaparin/administration & dosage , Heparin/administration & dosage , Heparin, Low-Molecular-Weight/administration & dosage , Humans , Inflammation , Interleukin 1 Receptor Antagonist Protein/administration & dosage , Kidney Diseases/complications , Kidney Transplantation , Lopinavir/administration & dosage , Pandemics , Renal Replacement Therapy , Renin-Angiotensin System , Ritonavir/administration & dosage , SARS-CoV-2
12.
Syst Rev ; 10(1): 243, 2021 09 07.
Article in English | MEDLINE | ID: covidwho-1398881

ABSTRACT

BACKGROUND: Conflicting findings and the analysis of unpublished and retracted data have led to controversy on the safety of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in people with COVID-19 infection. This meta-analysis examined the association of prescription of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) with the outcome from COVID-19. METHODS: A systematic search was conducted to find published studies that reported the outcome of COVID-19 in relation to prescription of ACEI or ARB. Two authors (MF and AD) independently screened and extracted data and assessed study quality and strength of association using standardised tools. The endpoints for the meta-analyses were severe or critical disease outcome and mortality based on standardised criteria. RESULTS: Twenty-six studies including 8389 people prescribed ACEI or ARB and 20,989 people not prescribed these medications were included. The quality of studies varied, and the overall strength of association was poor with a high risk of confounding bias. Patients prescribed ACEI or ARB had a greater prevalence of risk factors. Meta-analysis found an association between prescription of ACEI or ARB with severe or critical disease outcome (risk ratio, RR, 1.23, 95% confidence interval, CI, 1.06 to 1.42, p = 0.006, I2 = 88%) but this association was lost in sensitivity analyses. There was no association between ACEI or ARB prescription and mortality (RR 1.18, 95% CI 0.92 to 1.50, p = 0.19, I2 = 82%). CONCLUSIONS: This meta-analysis suggests that people prescribed ACEI or ARB more commonly had severe or critical disease outcome, but not mortality, in published cohorts of patients diagnosed with COVID-19. This finding is most likely due to a greater prevalence of risk factors in these patients rather than due to exposure to angiotensin pathway inhibitors.


Subject(s)
Angiotensin Receptor Antagonists , COVID-19 , Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Angiotensins , Humans , SARS-CoV-2
15.
Front Endocrinol (Lausanne) ; 12: 665134, 2021.
Article in English | MEDLINE | ID: covidwho-1305637

ABSTRACT

Introduction: Neuropilin-1(NRP1) is a cofactor that enhances SARS-CoV-2 coronavirus cell infectivity when co-expressed with angiotensin-converting enzyme 2(ACE2). The Renin-Angiotensin System (RAS) is activated in type 2 diabetes (T2D); therefore, the aim of this study was to determine if hypoglycaemia-induced stress in T2D would potentiate serum NRP1(sNRP1) levels, reflecting an increased risk for SARS-CoV-2 infection. Methods: A case-control study of aged-matched T2D (n = 23) and control (n = 23) subjects who underwent a hyperinsulinemic clamp over 1-hour to hypoglycemia(<40mg/dl) with subsequent timecourse of 4-hours and 24-hours. Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement determined RAS-related proteins: renin (REN), angiotensinogen (AGT), ACE2, soluble NRP1(sNRP1), NRP1 ligands (Vascular endothelial growth factor, VEGF and Class 3 Semaphorins, SEM3A) and NRP1 proteolytic enzyme (A Disintegrin and Metalloproteinase 9, ADAM9). Results: Baseline RAS overactivity was present with REN elevated and AGT decreased in T2D (p<0.05); ACE2 was unchanged. Baseline sNRP1, VEGF and ADAM9 did not differ between T2D and controls and remained unchanged in response to hypoglycaemia. However, 4-hours post-hypoglycemia, sNRP1, VEGF and ADAM9 were elevated in T2D(p<0.05). SEMA3A was not different at baseline; at hypoglycemia, SEMA3A decreased in controls only. Post-hypoglycemia, SEMA3A levels were higher in T2D versus controls. sNRP1 did not correlate with ACE2, REN or AGT. T2D subjects stratified according to ACE inhibitor (ACEi) therapies showed no difference in sNRP1 levels at either glucose normalization or hypoglycaemia. Conclusion: Hypoglycemia potentiated both plasma sNRP1 level elevation and its ligands VEGF and SEMA3A, likely through an ADAM9-mediated mechanism that was not associated with RAS overactivity or ACEi therapy; however, whether this is protective or promotes increased risk for SARS-CoV-2 infection in T2D is unclear. Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT03102801.


Subject(s)
ADAM Proteins/metabolism , Angiotensin-Converting Enzyme 2/metabolism , Diabetes Mellitus, Type 2/metabolism , Hypoglycemia/metabolism , Membrane Proteins/metabolism , Neuropilin-1/metabolism , Semaphorin-3A/metabolism , Vascular Endothelial Growth Factor A/metabolism , Aged , Angiotensins/metabolism , COVID-19 , Female , Glucose Clamp Technique , Humans , Male , Middle Aged , Protective Factors , Renin/metabolism , Risk Factors , SARS-CoV-2
16.
Rev Endocr Metab Disord ; 23(2): 151-170, 2022 04.
Article in English | MEDLINE | ID: covidwho-1290217

ABSTRACT

SARS-CoV-2, the virus responsible for COVID-19, uses angiotensin converting enzyme 2 (ACE2) as its primary cell-surface receptor. ACE2 is a key enzyme in the counter-regulatory pathway of the broader renin-angiotensin system (RAS) that has been implicated in a broad array of human pathology. The RAS is composed of two competing pathways that work in opposition to each other: the "conventional" arm involving angiotensin converting enzyme (ACE) generating angiotensin-2 and the more recently identified ACE2 pathway that generates angiotensin (1-7). Following the original SARS pandemic, additional studies suggested that coronaviral binding to ACE2 resulted in downregulation of the membrane-bound enzyme. Given the similarities between the two viruses, many have posited a similar process with SARS-CoV-2. Proponents of this ACE2 deficiency model argue that downregulation of ACE2 limits its enzymatic function, thereby skewing the delicate balance between the two competing arms of the RAS. In this review we critically examine this model. The available data remain incomplete but are consistent with the possibility that the broad multisystem dysfunction of COVID-19 is due in large part to functional ACE2 deficiency leading to angiotensin imbalance with consequent immune dysregulation and endothelial cell dysfunction.


Subject(s)
Angiotensin-Converting Enzyme 2 , Angiotensins , COVID-19 , Angiotensin-Converting Enzyme 2/deficiency , COVID-19/physiopathology , Humans , Pandemics , Renin-Angiotensin System , SARS-CoV-2
17.
Med Clin (Barc) ; 158(7): 315-323, 2022 Apr 08.
Article in English, Spanish | MEDLINE | ID: covidwho-1258460

ABSTRACT

BACKGROUND: Hypertension is a prevalent condition among SARS-CoV-2 infected patients. Whether renin-angiotensin-aldosterone system (RAAS) inhibitors are beneficial or harmful is controversial. METHODS: We have performed a national retrospective, nonexperimental comparative study from two tertiary hospitals to evaluate the impact of chronic use of RAAS inhibitors in hypertensive COVID-19 patients. A meta-analysis was performed to strengthen our findings. RESULTS: Of 849 patients, 422 (49.7%) patients were hypertensive and 310 (73.5%) were taking RAAS inhibitors at baseline. Hypertensive patients were older, had more comorbidities, and a greater incidence of respiratory failure (-0.151 [95% CI -0.218, -0.084]). Overall mortality in hypertensive patients was 28.4%, but smaller among those with prescribed RAAS inhibitors before (-0.167 [95% CI -0.220, -0.114]) and during hospitalization (0.090 [-0.008,0.188]). Similar findings were observed after two propensity score matches that evaluated the benefit of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers among hypertensive patients. Multivariate logistic regression analysis of hypertensive patients found that age, diabetes mellitus, C-reactive protein, and renal failure were independently associated with all-cause mortality. On the contrary, ACEIs decreased the risk of death (OR 0.444 [95% CI 0.224-0.881]). Meta-analysis suggested a protective benefit of RAAS inhibitors (OR 0.6 [95% CI 0.42-0.8]) among hypertensive COVID-19. CONCLUSION: Our data suggest that RAAS inhibitors may play a protective role in hypertensive COVID-19 patients. This finding was supported by a meta-analysis of the current evidence. Maintaining these medications during hospital stay may not negatively affect COVID-19 outcomes.


Subject(s)
COVID-19 , Hypertension , Aldosterone/pharmacology , Aldosterone/therapeutic use , Angiotensin Receptor Antagonists/pharmacology , Angiotensin Receptor Antagonists/therapeutic use , Angiotensins/pharmacology , Angiotensins/therapeutic use , Antihypertensive Agents/therapeutic use , Humans , Hypertension/complications , Hypertension/drug therapy , Mineralocorticoid Receptor Antagonists/therapeutic use , Registries , Renin/pharmacology , Renin/therapeutic use , Renin-Angiotensin System , Retrospective Studies , SARS-CoV-2
18.
J Cardiovasc Med (Hagerstown) ; 23(1): 1-11, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1259311

ABSTRACT

2020 marked the 20th anniversary of the discovery of the angiotensin-converting enzyme 2 (ACE2). This major event that changed the way we see the renin-angiotensin system today could have passed quietly. Instead, the discovery that ACE2 is a major player in the severe acute respiratory syndrome coronavirus 2 pandemic has blown up the literature regarding this enzyme. ACE2 connects the classical arm renin-angiotensin system, consisting mainly of angiotensin II peptide and its AT1 receptor, with a protective arm, consisting mainly of the angiotensin 1-7 peptide and its Mas receptor. In this brief article, we have reviewed the literature to describe how ACE2 is a key protective arm enzyme in the function of many organs, particularly in the context of brain and cardiovascular function, as well as in renal, pulmonary and digestive homeostasis. We also very briefly review and refer to recent literature to present an insight into the role of ACE2 in determining the course of coronavirus diseases 2019.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Renin-Angiotensin System/physiology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensins/physiology , Animals , COVID-19/complications , COVID-19/metabolism , COVID-19/virology , Humans , Mice , Organ Specificity , Rats , Receptors, Angiotensin/physiology , Renin-Angiotensin System/drug effects , SARS-CoV-2/metabolism
19.
Int J Mol Sci ; 22(9)2021 Apr 26.
Article in English | MEDLINE | ID: covidwho-1201444

ABSTRACT

SARS-CoV-2 impairs the renin-angiotensin-aledosterone system via binding ACE2 enzyme. ACE2 plays a key role in the biosynthesis of angiotensin (1-7), catalyzing the conversion of angiotensin 2 into angiotensin (1-7) and the reaction of angiotensin synthesis (1-9), from which angiotensin is (1-7) produced under the influence of ACE (Angiotensin-Converting Enzyme). Angiotensin 2 is a potent vasoconstrictor and atherogenic molecule converted by ACE2 to reducing inflammation and vasodilating in action angiotensin (1-7). Angiotensin (1-9), that is a product of angiotensin 1 metabolism and precursor of angiotensin (1-7), also exerts cell protective properties. Balance between angiotensin 2 and angiotensin (1-7) regulates blood pressure and ACE2 plays a critical role in this balance. ACE2, unlike ACE, is not inhibited by ACE inhibitors at the doses used in humans during the treatment of arterial hypertension. Membrane ACE2 is one of the receptors that allows SARS-CoV-2 to enter the host cells. ACE2 after SARS-CoV-2 binding is internalized and degraded. Hence ACE2 activity on the cell surface is reduced leading to increase the concentration of angiotensin 2 and decrease the concentration of angiotensin (1-7). Disturbed angiotensins metabolism, changes in ratio between angiotensins with distinct biological activities leading to domination of atherogenic angiotensin 2 can increase the damage to the lungs.


Subject(s)
COVID-19/pathology , Renin-Angiotensin System/physiology , SARS-CoV-2/metabolism , Angiotensin-Converting Enzyme 2/metabolism , Angiotensins/metabolism , COVID-19/virology , Humans , Peptidyl-Dipeptidase A/metabolism , SARS-CoV-2/isolation & purification , Virus Internalization
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