scholarly journals Metabolomics and computational analysis of the role of monoamine oxidase activity in delirium and SARS-COV-2 infection

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Miroslava Cuperlovic-Culf ◽  
Emma L. Cunningham ◽  
Hossen Teimoorinia ◽  
Anuradha Surendra ◽  
Xiaobei Pan ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Metabolic Networks ◽  
Protein Docking ◽  
Docking Analysis ◽  
Angiotensin Converting Enzyme 2 ◽  
Distance Correlation ◽  
Metabolomic Profiling ◽  
Postoperative Setting ◽  
Significant Concentration

AbstractDelirium is an acute change in attention and cognition occurring in ~ 65% of severe SARS-CoV-2 cases. It is also common following surgery and an indicator of brain vulnerability and risk for the development of dementia. In this work we analyzed the underlying role of metabolism in delirium-susceptibility in the postoperative setting using metabolomic profiling of cerebrospinal fluid and blood taken from the same patients prior to planned orthopaedic surgery. Distance correlation analysis and Random Forest (RF) feature selection were used to determine changes in metabolic networks. We found significant concentration differences in several amino acids, acylcarnitines and polyamines linking delirium-prone patients to known factors in Alzheimer’s disease such as monoamine oxidase B (MAOB) protein. Subsequent computational structural comparison between MAOB and angiotensin converting enzyme 2 as well as protein–protein docking analysis showed that there potentially is strong binding of SARS-CoV-2 spike protein to MAOB. The possibility that SARS-CoV-2 influences MAOB activity leading to the observed neurological and platelet-based complications of SARS-CoV-2 infection requires further investigation.

scholarly journals Metabolomics and Computational Analysis of the Role of Monoamine Oxidase Activity in Delirium and SARS-COV-2 Infection

2021 ◽  
Author(s):  
Miroslava Cuperlovic-Culf ◽  
Emma L. Cunningham ◽  
Hossen Teimoorinia ◽  
Anu Surendra ◽  
Xiaobei Pan ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Metabolic Networks ◽  
Protein Docking ◽  
Docking Analysis ◽  
Angiotensin Converting Enzyme 2 ◽  
Distance Correlation ◽  
Metabolomic Profiling ◽  
Postoperative Setting ◽  
Significant Concentration

Abstract Delirium is an acute change in attention and cognition occurring in ~65% of severe SARS-CoV-2 cases. It is also common following surgery and an indicator of brain vulnerability and risk for the development of dementia. In this work we analyzed the underlying role of metabolism in delirium-susceptibility in the postoperative setting using metabolomic profiling of cerebrospinal fluid and blood taken from the same patients prior to planned orthopaedic surgery. Distance correlation analysis and Random Forest (RF) feature selection were used to determine changes in metabolic networks. We found significant concentration 2 differences in several amino acids, acylcarnitines and polyamines linking delirium-prone patients to known factors in Alzheimer’s disease such as monoamine oxidase B (MAOB) protein. Subsequent computational structural comparison between MAOB and angiotensin converting enzyme 2 as well as protein-protein docking analysis showed that there potentially is strong binding of SARS-CoV-2 spike protein to MAOB. The possibility that SARS-CoV-2 influences MAOB activity leading to the observed neurological and platelet-based complications of SARS-CoV-2 infection requires further investigation.

Role of key point Mutations in Receptor Binding Domain of SARS-CoV-2 Spike Glycoprotein

2020 ◽  
Vol 20 ◽  
Author(s):  
Bipin Singh
Keyword(s):  
Receptor Binding ◽  
Point Mutations ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein ◽  
Angiotensin Converting Enzyme 2 ◽  
Recent Outbreak ◽  
Novel Coronavirus ◽  
Genomic Similarity

: The recent outbreak of novel coronavirus (SARS-CoV-2 or 2019-nCoV) and its worldwide spread is posing one of the major threats to human health and the world economy. It has been suggested that SARS-CoV-2 is similar to SARSCoV based on the comparison of the genome sequence. Despite the genomic similarity between SARS-CoV-2 and SARSCoV, the spike glycoprotein and receptor binding domain in SARS-CoV-2 shows the considerable difference compared to SARS-CoV, due to the presence of several point mutations. The analysis of receptor binding domain (RBD) from recently published 3D structures of spike glycoprotein of SARS-CoV-2 (Yan, R., et al. (2020); Wrapp, D., et al. (2020); Walls, A. C., et al. (2020)) highlights the contribution of a few key point mutations in RBD of spike glycoprotein and molecular basis of its efficient binding with human angiotensin-converting enzyme 2 (ACE2).

scholarly journals Role of Tissue Factor in the Pathogenesis of COVID-19 and the Possible Ways to Inhibit It

2021 ◽  
Vol 27 ◽  
pp. 107602962110039
Author(s):  
Carlos A. Cañas ◽  
Felipe Cañas ◽  
Mario Bautista-Vargas ◽  
Fabio Bonilla-Abadía
Keyword(s):  
Tissue Factor ◽  
Proinflammatory Cytokines ◽  
Antiphospholipid Antibodies ◽  
Therapeutic Strategies ◽  
Prothrombotic State ◽  
Pulmonary Epithelium ◽  
Angiotensin Converting Enzyme 2 ◽  
Patients With Heart Failure ◽  
Inflammatory Effect

COVID-19 (Coronavirus Disease 2019) is a highly contagious infection and associated with high mortality rates, primarily in elderly; patients with heart failure; high blood pressure; diabetes mellitus; and those who are smokers. These conditions are associated to increase in the level of the pulmonary epithelium expression of angiotensin-converting enzyme 2 (ACE-2), which is a recognized receptor of the S protein of the causative agent SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). Severe cases are manifested by parenchymal lung involvement with a significant inflammatory response and the development of microvascular thrombosis. Several factors have been involved in developing this prothrombotic state, including the inflammatory reaction itself with the participation of proinflammatory cytokines, endothelial dysfunction/endotheliitis, the presence of antiphospholipid antibodies, and possibly the tissue factor (TF) overexpression. ARS-Cov-19 ACE-2 down-regulation has been associated with an increase in angiotensin 2 (AT2). The action of proinflammatory cytokines, the increase in AT2 and the presence of antiphospholipid antibodies are known factors for TF activation and overexpression. It is very likely that the overexpression of TF in COVID-19 may be related to the pathogenesis of the disease, hence the importance of knowing the aspects related to this protein and the therapeutic strategies that can be derived. Different therapeutic strategies are being built to curb the expression of TF as a therapeutic target for various prothrombotic events; therefore, analyzing this treatment strategy for COVID-19-associated coagulopathy is rational. Medications such as celecoxib, cyclosporine or colchicine can impact on COVID-19, in addition to its anti-inflammatory effect, through inhibition of TF.

Combined 3D-QSAR and docking analysis for the design and synthesis of chalcones as potent and selective monoamine oxidase B inhibitors

2021 ◽  
Vol 108 ◽  
pp. 104689
Author(s):  
Marco Mellado ◽  
César González ◽  
Jaime Mella ◽  
Luis F. Aguilar ◽  
Dolores Viña ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
3D Qsar ◽  
Monoamine Oxidase B ◽  
Docking Analysis ◽  
Design And Synthesis

ROLE OF AN ENDOGENOUS MONOAMINE OXIDASE INHIBITOR, ISATIN, IN SHRSP BRAIN

1995 ◽  
Vol 22 (s1) ◽  
pp. S86-S87 ◽  
Author(s):  
N. Hamaue ◽  
T. Endo ◽  
M. Hirafuji ◽  
N. Yamazaki ◽  
H. Togashi ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Monoamine Oxidase Inhibitor ◽  
Oxidase Inhibitor

scholarly journals Evidence for a role of angiotensin converting enzyme 2 in proteinuria of idiopathic nephrotic syndrome

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Roberta da Silva Filha ◽  
Sérgio Veloso Brant Pinheiro ◽  
Thiago Macedo e Cordeiro ◽  
Victor Feracin ◽  
Érica Leandro Marciano Vieira ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Idiopathic Nephrotic Syndrome ◽  
Renin Angiotensin System ◽  
Cross Sectional Study ◽  
Healthy Controls ◽  
Ang Ii ◽  
Cross Sectional ◽  
Angiotensin Converting Enzyme 2 ◽  
Inflammatory Molecules

AbstractIntroduction: Renin angiotensin system (RAS) plays a role in idiopathic nephrotic syndrome (INS). Most studies investigated only the classical RAS axis. Therefore, the aims of the present study were to evaluate urinary levels of RAS molecules related to classical and to counter-regulatory axes in pediatric patients with INS, to compare the measurements with levels in healthy controls and to search for associations with inflammatory molecules, proteinuria and disease treatment. Subjects and methods: This cross-sectional study included 31 patients with INS and 19 healthy controls, matched for age and sex. Patients and controls were submitted to urine collection for measurement of RAS molecules [Ang II, Ang-(1-7), ACE and ACE2] by enzyme immunoassay and cytokines by Cytometric Bead Array. Findings in INS patients were compared according to proteinuria: absent (<150 mg/dl, n = 15) and present (≥150 mg/dl, n = 16). Results: In comparison to controls, INS patients had increased Ang II, Ang-(1-7) and ACE, levels while ACE2 was reduced. INS patients with proteinuria had lower levels of ACE2 than those without proteinuria. ACE2 levels were negatively correlated with 24-h-proteinuria. Urinary concentrations of MCP-1/CCL2 were significantly higher in INS patients, positively correlated with Ang II and negatively with Ang-(1-7). ACE2 concentrations were negatively correlated with IP-10/CXCL-10 levels, which, in turn, were positively correlated with 24-h-proteinuria. Conclusion: INS patients exhibited changes in RAS molecules and in chemokines. Proteinuria was associated with low levels of ACE2 and high levels of inflammatory molecules.

scholarly journals Bioinformatics analysis of the structural and evolutionary characteristics for toll-like receptor 15

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2079 ◽  
Author(s):  
Jinlan Wang ◽  
Zheng Zhang ◽  
Fen Chang ◽  
Deling Yin
Keyword(s):  
Convex Surface ◽  
Purifying Selection ◽  
Structural Features ◽  
Protein Docking ◽  
Activation Process ◽  
Docking Analysis ◽  
Unique Role ◽  
Evolutionarily Conserved ◽  
Interaction Interface ◽  
Tir Domains

Toll-like receptors (TLRs) play important role in the innate immune system. TLR15 is reported to have a unique role in defense against pathogens, but its structural and evolution characterizations are still poorly understood. In this study, we identified 57 completed TLR15 genes from avian and reptilian genomes. TLR15 clustered into an individual clade and was closely related to family 1 on the phylogenetic tree. Unlike the TLRs in family 1 with the broken asparagine ladders in the middle, TLR15 ectodomain had an intact asparagine ladder that is critical to maintain the overall shape of ectodomain. The conservation analysis found that TLR15 ectodomain had a highly evolutionarily conserved region on the convex surface of LRR11 module, which is probably involved in TLR15 activation process. Furthermore, the protein–protein docking analysis indicated that TLR15 TIR domains have the potential to form homodimers, the predicted interaction interface of TIR dimer was formed mainly by residues from the BB-loops andαC-helixes. Although TLR15 mainly underwent purifying selection, we detected 27 sites under positive selection for TLR15, 24 of which are located on its ectodomain. Our observations suggest the structural features of TLR15 which may be relevant to its function, but which requires further experimental validation.

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