Corpus overview


MeSH Disease

Human Phenotype


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    SARS-CoV-2 Spike protein binds to bacterial lipopolysaccharide and boosts proinflammatory activity

    Authors: Ganna Petruk; Manoj Puthia; Jitka Petrlova; Ann-Charlotte Strömdahl; Sven Kjellström; Artur Schmidtchen

    doi:10.1101/2020.06.29.175844 Date: 2020-06-29 Source: bioRxiv

    ABSTRACTThere is a well-known and established link between high lipopolysaccharide (LPS) levels in blood SERO and the metabolic syndrome MESHD (MS). MS is a risk factor for developing severe COVID-19 and acute respiratory distress HP syndrome MESHD (ARDS). Here we define an interaction between SARS-CoV-2 Spike (S) protein and LPS and its link to aggravated inflammation MESHD in vitro and in vivo. Electrophoresis under native conditions demonstrated that SARS-CoV-2 S protein binds to Escherichia coli LPS, forming high molecular weight aggregates. Microscale thermophoresis analysis further defined the interaction, having a KD of ~47 nM, similar to the observed affinity between LPS and the human receptor CD14. Moreover, S protein, when combined with low levels of LPS, boosted nuclear factor-kappa B (NF-κB) and cytokine responses in monocytic THP-1 cells and human blood SERO, respectively. In an experimental model of localized inflammation MESHD, employing NF-κB reporter mice and in vivo bioimaging, S protein in conjunction with LPS significantly increased the inflammatory response HP when compared with S protein and LPS alone. Apart from providing information on LPS as a ligand for S protein, our results are of relevance for studies on comorbidities involving bacterial endotoxins, such as the MS, or co-existing acute and chronic infections HP infections MESHD in COVID-19 patients.Competing Interest StatementA.S is a founder and shareholder of in2cure AB, a company developing therapies based on host defense peptides. A patent application related to the present work, with A.S. and G.P. listed as inventors, has been filed.AbbreviationsARDSacute respiratory distress HP syndromeCOVID-19coronavirus disease MESHD 2019MSmetabolic syndromeLBPLPS-binding proteinLPSlipopolysaccharideNF-κBnuclear factor-kappa BSARS-CoV-2 Spike proteinS proteinTLR4Toll-like receptor 4View Full Text

    Pyridoxal 5'-phosphate to mitigate immune dysregulation HP and coagulopathy in COVID-19

    Authors: Julie Desbarats

    id:10.20944/preprints202005.0144.v1 Date: 2020-05-08 Source:

    Although most cases of COVID-19 are paucisymptomatic, severe disease MESHD is characterized by immune dysregulation HP, with a decreased type I interferon response, increased inflammatory HP indicators, surging IL-6, IL-10 and TNFα suggestive of cytokine storm, progressive lymphopenia MESHD lymphopenia HP, and abnormal blood SERO clotting. Factors determining susceptibility to severe disease MESHD are poorly understood, although mortality correlates with increasing age TRANS and co-morbidities including diabetes and cardiovascular disease MESHD (CVD). Pyridoxal 5'-phosphate (PLP) tends to be insufficient in populations particularly vulnerable to COVID-19, including the elderly TRANS, the institutionalized, and people with diabetes and CVD, and PLP becomes further depleted during infection MESHD and inflammation MESHD. In turn, low PLP results in immune imbalance, as PLP is an essential cofactor in pathways regulating cytokine production, in particular type I interferons and IL-6, and in lymphocyte trafficking and endothelial integrity. Furthermore, normalizing PLP levels attenuates abnormalities in platelet aggregation and clot formation. Finally, PLP insufficiency induces excess secretion of renin and angiotensin, and hypertension MESHD hypertension HP. In inflammatory disease MESHD, pharmacological doses of PLP decrease circulating TNFα, IL-6 and D-dimer, and animal studies demonstrate that supplemental PLP shortens the duration and severity of viral pneumonia MESHD pneumonia HP. Severe COVID-19 manifests as an imbalance in the immune response and the clotting system. Pharmacological PLP supplementation may therefore mitigate COVID-19 symptoms by alleviating both the immune suppression underlying viral spread and the pathological hypersecretion of inflammatory cytokines, as well as directly bolstering endothelial integrity and preventing hypercoagulability HP.

    Release of potential pro-inflammatory peptides from SARS-CoV-2 spike glycoproteins in neutrophil-extracellular traps

    Authors: Aitor Blanco-Miguez; Borja Sanchez

    doi:10.1101/2020.05.02.072439 Date: 2020-05-02 Source: bioRxiv

    COVID-2019 has progressed in around 10-15% of patients to an acute respiratory distress HP syndrome MESHD characterized by extensive pulmonary inflammation MESHD and elevated production of pro-inflammatory cytokines. Neutrophil activation seems to be crucial in the initiation and perpetuation of this exacerbated lung inflammation MESHD. However, the precise mechanisms by which this activation occurs remain yet elusive. To this end, this in silico study tried to identify potential proinflammatory inducing peptides (PIPs) produced by the action of the elastase released in neutrophil-extracellular traps over SARS-CoV-2 particles. We found nine potential PIPs exclusive from the SARS-CoV-2, showing homology against T cell recognition epitopes. Moreover, 78 percent of these exclusive PIPs were found produced by the enzymatic cleavage on the spike glycoproteins, suggesting that high PIP concentrations might be released following SARS-CoV-2 huge replication rate. Therefore, these PIPs might play a role in the exacerbated inflammatory response observed in some patients. HighlightsO_LINine potential PIPs were predicted exclusive from the SARS-CoV-2. C_LIO_LISARS-CoV-2 PIPs showed homology against T cell recognition epitopes. C_LIO_LIMost of PIPs were produced by enzymatic cleavage of the spike glycoproteins. C_LIO_LIThe release of these PIPs might be related to the increased inflammatory response HP observed in the patients. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=189 SRC="FIGDIR/small/072439v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@1cd2c3forg.highwire.dtl.DTLVardef@113f8b7org.highwire.dtl.DTLVardef@2df78eorg.highwire.dtl.DTLVardef@1d7c946_HPS_FORMAT_FIGEXP M_FIG C_FIG

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MeSH Disease
Human Phenotype

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