Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins


SARS-CoV-2 Proteins
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    SARS-CoV-2 infects blood MESHD monocytes to activate NLRP3 HGNC and AIM2 HGNC inflammasomes, pyroptosis and cytokine release

    Authors: Caroline Junqueira; Angela Crespo; Shahin Ranjbar; Jacob Ingber; Blair Parry; Sagi David; Luna B de Lacerda; Mercedes Lewandrowski; Sarah Alden Clark; Felicia Ho; Setu Vora; Valerie Leger; Caroline Beackes; Justin Margolin; Nicole Russell; Lee Gehrke; Upasana Das Adhikari; Lauren Henderson; Erin Janssen; Douglas Kwon; Chris Sander; Jonathan Abraham; Michael Filbin; Marcia B. Goldberg; Hao Wu; Mehta Gautam; Steven Bell; Anne Goldfeld; Judy Lieberman

    doi:10.1101/2021.03.06.21252796 Date: 2021-03-08 Source: medRxiv

    SARS-CoV-2 causes acute respiratory distress that can progress to multiorgan failure MESHD and death MESHD in some patients. Although severe COVID-19 MESHD disease is linked to exuberant inflammation MESHD, how SARS-CoV-2 triggers inflammation MESHD is not understood. Monocytes are sentinel blood cells that sense invasive infection MESHD to form inflammasomes that activate caspase-1 HGNC and gasdermin D HGNC ( GSDMD HGNC GSDMD MESHD) pores, leading to inflammatory death MESHD (pyroptosis) and processing and release of IL-1 family cytokines, potent inflammatory mediators. Here we show that ~10% of blood monocytes in COVID-19 MESHD patients are dying and infected with SARS-CoV-2. Monocyte infection, which depends on antiviral antibodies, activates NLRP3 HGNC and AIM2 HGNC inflammasomes, caspase-1 HGNC and GSDMD HGNC cleavage and relocalization. Signs of pyroptosis (IL-1 family cytokines, LDH) in the plasma correlate with development of severe disease. Moreover, expression quantitative trait loci (eQTLs) linked to higher GSDMD HGNC expression increase the risk of severe COVID-19 MESHD disease (odds ratio, 1.3, p<0.005). These findings taken together suggest that antibody-mediated SARS-CoV-2 infection MESHD of monocytes triggers inflammation MESHD that contributes to severe COVID-19 MESHD disease pathogenesis.

    Targeting of the NLRP3 HGNC Inflammasome for early COVID-19 MESHD

    Authors: Carlo Marchetti; Kara Mould; Isak W. Tengesdal; William J. Janssen; Charles A. Dinarello

    doi:10.1101/2021.02.24.432734 Date: 2021-02-24 Source: bioRxiv

    Following entry and replication of Severe Acute Respiratory Syndrome-coronavirus MESHD 2 (SARS-CoV-2) into ACE2 expressing cells, the infected cells undergo lysis releasing more virus but also cell contents. In the lung, constitutive cytokines such as IL-1 HGNC are released together with other cell contents. A cascade of inflammatory cytokines ensues, including chemokines and IL-1{beta}, triggering both local as well as systemic inflammation MESHD. This cascade of inflammatory cytokines in patients with COVID-19 MESHD is termed Cytokine Release Syndrome ( CRS MESHD), and is associated with poor outcomes and death MESHD. Many studies reveal that blocking IL-1{beta HGNC} activities in COVID-19 MESHD patients reduces disease severity and deaths MESHD. Here we report highly significant circulating levels of IL-1{beta HGNC}, IL-1 Receptor antagonist HGNC, IL-6 HGNC, TNF HGNC, IL-10 HGNC and soluble urokinase plasminogen activator receptor HGNC in COVID-19 MESHD patients with mild or no symptoms. We also report that in circulating myeloid cells from the same patients, there is increased expression of the NOD-, LRR- and pyrin domain-containing 3 ( NLRP3 HGNC) early in the infection. We observed increased NLRP3 HGNC gene expression in myeloid cells correlated with IL-1{beta HGNC} gene expression and also with elevated circulating IL-1{beta HGNC} levels. We conclude that early in SARS-CoV-2 infection MESHD, NLRP3 HGNC activation takes place and initiates the CRS. Thus, NLRP3 HGNC is a target to reduce the organ damage of inflammatory cytokines of the CRS.

    Exaggerated cytokine production in human peripheral blood mononuclear cells by recombinant SARS-CoV-2 spike PROTEIN glycoprotein S1 and its inhibition by dexamethasone

    Authors: Olumayokun A Olajide; Victoria U Iwuanyanwu; Izabela Lepiarz-Raba; Alaa A Al-Hindawi

    doi:10.1101/2021.02.03.429536 Date: 2021-02-03 Source: bioRxiv

    An understanding of the pathological inflammatory mechanisms involved in SARS CoV-2 virus infection MESHD is necessary in order to discover new molecular pharmacological targets for SARS-CoV-2 spike PROTEIN glycoprotein. In this study, the effects of a recombinant SARS CoV-2 spike PROTEIN glycoprotein S1 was investigated in human peripheral blood mononuclear cells (PBMCs). Stimulation with spike glycoprotein S1 PROTEIN (100 ng/mL) resulted in significant elevation in the production of TNF HGNC, IL-6 HGNC, IL-1{beta HGNC} and IL-8 HGNC. However, pre-treatment with dexamethasone (100 nM) caused a significant reduction in the release of these cytokines. Further experiments revealed that S1 stimulation of PBMCs increased phosphorylation of NF-{kappa}B HGNC p65 HGNC and I{kappa}B, while increasing I{kappa}B degradation. DNA binding of NF-{kappa}B HGNC p65 HGNC was also significantly increased following stimulation with S1. Treatment of PBMCs with dexamethasone (100 nM) or BAY11-7082 (1 M) resulted in inhibition of S1-induced NF-{kappa}B HGNC activation. Activation of p38 HGNC MAPK by S1 was blocked in the presence of dexamethasone and SKF 86002. CRID3, but not dexamethasone pre-treatment produced significant inhibition of S1-induced activation of NLRP3 HGNC/ caspase 1 HGNC. Further experiments revealed that S1-induced increase in the production of TNF HGNC, IL-6 HGNC, IL-1{beta HGNC} and IL-8 HGNC was reduced in the presence of BAY11-7082 and SKF 86002, while CRID3 pre-treatment resulted in the reduction of IL-1{beta HGNC} production. These results suggest that SARS-CoV-2 spike PROTEIN glycoprotein S1 stimulate PBMCs to release pro inflammatory cytokines through mechanisms involving activation of NF-{kappa}B HGNC, p38 MAPK and NLRP3 HGNC inflammasome. It is proposed that clinical benefits of dexamethasone in COVID-19 MESHD is possibly due to its anti-inflammatory activity in reducing SARS-CoV-2 cytokine storm.

    SARS-CoV-2 spike PROTEIN glycoprotein S1 induces neuroinflammation in BV-2 microglia

    Authors: Olumayokun A Olajide; Victoria U Iwuanyanwu; Oyinkansola D Adegbola; Oliver Artz; Daniele Rosado; Tara Skopelitis; Munenori Kitagawa; Ullas V Pedmale; David Jackson

    doi:10.1101/2020.12.29.424619 Date: 2020-12-29 Source: bioRxiv

    The emergence of SARS-CoV-2 has resulted in a global pandemic. In addition to respiratory complications as a result of SARS-CoV-2 illness MESHD, accumulating evidence suggests that neurological and neuropsychiatric symptoms MESHD are associated with the disease caused by the virus. In this study, we investigated the effects of the SARS-CoV-2 spike PROTEIN glycoprotein S1 stimulation on neuroinflammation in BV-2 microglia. Analyses of culture supernatants revealed an increase in the production of TNF HGNC, IL-6 HGNC, IL-1{beta HGNC} and iNOS HGNC/NO. SARS-CoV-2 spike PROTEIN glycoprotein S1 increased protein expressions of phospho-p65 and phospho-I{kappa}B, as well as enhancing DNA binding and transcriptional activity of NF-{kappa}B HGNC. Pro-inflammatory effects of the glycoprotein effects were reduced in the presence of BAY11-7082 (1 M). The presence of SARS-CoV-2 spike PROTEIN glycoprotein S1 in BV-2 microglia increased the protein expression of NLRP3 HGNC, as well as caspase-1 HGNC activity. However, pre-treatment with CRID3 (1 M) or BAY11-7082 (1 M) resulted in the inhibition of NLRP3 HGNC inflammasome/ caspase-1 HGNC. It was also observed that CRID3 attenuated SARS-CoV-2 spike PROTEIN glycoprotein S1-induced increase in IL-1{beta HGNC} production. Increased protein expression of p38 MAPK was observed in BV-2 microglia stimulated with the spike glycoprotein S1 PROTEIN, and was reduced in the presence of SKF 86002. These results have provided the first evidence demonstrating SARS-CoV-2 spike PROTEIN S1 glycoprotein-induced neuroinflammation in BV-2 microglia. We propose that promotion of neuroinflammation by this glycoprotein is mediated through activation of NF-{kappa}B HGNC, NLRP3 HGNC inflammasome and p38 MAPK. These results are significant because of their relevance to our understanding of neurological and neuropsychiatric symptoms MESHD observed in patients infected with SARS-CoV-2.

    PNPLA3 HGNC and TLL-1 HGNC polymorphisms affect disease severity in patients with COVID-19 MESHD 

    Authors: Stefania Grimaudo; Emanuele Amodio; Rosaria Maria Pipitone; Carmelo Massimo Maida; Stefano Pizzo; Tullio Prestileo; Fabio Tramuto; Davide Sardina; Francesco Vitale; Alessandra Casuccio; Antonio Craxì

    doi:10.21203/ Date: 2020-07-07 Source: ResearchSquare

    Introduction Albeit the pathogenesis of COVID-19 MESHD remains unclear, host’s genetic polymorphisms in genes i nfection MESHDand reinfection, i nflammation, MESHD or immune stimulation could play a role in determining the course and outcome. Methods We studied in the early phase of pandemic consecutive patients (N=383) with SARS-CoV-2 infection MESHD ARS-CoV-2 infection, MESHD whose subsequent clinical course was classified as mild or severe, the latter being characterised by admission to intensive therapy unit or d eath. MESHD Five host gene polymorphisms (M ERTK HGNCrs4374383, P NPLA3 HGNCrs738409, T LL-1 HGNCrs17047200, I FNL3 HGNCrs1297860, and INFL4 rs368234815) were assessed by using whole nucleic acids extracted from nasopharyngeal swabs. Specific protease cleavage sites of T LL-1 HGNCon the SARS-CoV-2 Spyke protein were predicted in silico. Results Male subjects and older patients were significantly at higher risk for a severe outcome (p=0.02 and p<0.001, respectively). By considering patients ≤ 65 years, after adjusting for potential confounding due to sex, an increased risk of severe outcome was found in subjects with the GG genotype of P NPLA3 HGNC(adj-OR: 4.69; 95% CI= 1.01-22.04) or TT genotype of T LL-1 HGNC(adj-OR=9.1; 95% CI= 1.45-57.3). In silico evaluation showed that T LL-1 HGNCis potentially involved in the Spike protein PROTEIN cleavage.Discussion Subjects carrying a GG genotype in P NPLA3 HGNCgene might have a constitutive upregulation of the N LRP3 HGNCinflammosome and be more prone to tissue damage when infected by SARS-CoV-2. The TT genotype in T LL-1 HGNCgene might affect its protease activity on the SARS-CoV-2 Spyke protein, enhancing the ability to i nfect MESHDor re-infect host’s cells. The untoward effect of these variants on disease course is evident in younger patients due to the relative absence of comorbidities as determinants of prognosis.

    Network analysis of Down syndrome and SARS-CoV-2 identifies risk and protective factors for COVID-19 MESHD

    Authors: Ilario De Toma; Mara Dierssen

    doi:10.21203/ Date: 2020-06-11 Source: ResearchSquare

    Background: SARS-CoV-2 has spread uncontrollably worldwide while we still ignore how particularly vulnerable populations, such as Down syndrome ( DS MESHD) individuals are affected by the COVID-19 pandemic MESHD COVID-19 pandemic MESHD. Individuals with DS have more risk of infections with respiratory complications MESHD and present signs of auto-inflammation MESHD. They also suffer from multiple comorbidities that are associated with poorer COVID-19 MESHD prognosis in the general population. All this might place DS individuals at higher risk of SARS-CoV-2 infection MESHD or poorer clinical outcomes.Methods: In order to get insight into the interplay between DS genes and SARS-cov2 infection MESHD and pathogenesis we retrieved the genes belonging to the molecular pathways involved in COVID-19 MESHD and the host proteins interacting with viral proteins from SARS-CoV-2. We therefore analyzed the overlaps of these genes with HSA21 genes, HSA21 interactors and other genes consistently differentially expressed in DS (using public transcriptomic datasets) creating a DS-SARS-CoV-2 network.Results: We detected COVID-19 MESHD protective and risk factors that might affect the susceptibility of individuals with DS both at the infection stage and in the progression to acute respiratory distress syndrome MESHD.Conclusion: Our analysis suggests that at the infection stage DS individuals might be more susceptible to infection due to triplication of TMPRSS2 HGNC, that primes the viral S protein PROTEIN for entry in the host cells, even though the anti-viral interferon I signaling is upregulated in DS and this might increase the initial anti-viral response. In the second pro-inflammatory immunopathogenic phase of the infection, the prognosis for DS patients might worsen due to upregulation of inflammatory genes that might favor the typical cytokine storm of COVID-19 MESHD. We also detected strong downregulation of the NLRP3 HGNC gene, critical for maintenance of homeostasis against pathogenic infections, possibly leading to bacterial infection complications MESHD.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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