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HGNC Genes

SARS-CoV-2 proteins

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SARS-CoV-2 Proteins
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    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.

    Natural Killer cell activation, reduced ACE2 HGNC, TMPRSS2 HGNC, cytokines G-CSF HGNC, M-CSF HGNC and SARS-CoV-2-S pseudovirus infectivity by MEK HGNC inhibitor treatment of human cells

    Authors: Lanlan Zhou; Kelsey Huntington; Shengliang Zhang; Lindsey Carlsen; Eui-Young So; Cassandra Parker; Ilyas Sahin; Howard Safran; Suchitra Kamle; Chang-Min Lee; Chun-Geun Lee; Jack A. Elias; Kerry S. Campbell; Mandar T. Naik; Walter J. Atwood; Emile Youssef; Jonathan A. Pachter; Arunasalam Navaraj; Attila A. Seyhan; Olin Liang; Wafik El-Deiry

    doi:10.1101/2020.08.02.230839 Date: 2020-08-03 Source: bioRxiv

    COVID-19 MESHD affects vulnerable populations including elderly individuals and patients with cancer MESHD. Natural Killer (NK) cells and innate-immune TRAIL HGNC suppress transformed and virally-infected cells. ACE2 HGNC, and TMPRSS2 HGNC protease promote SARS-CoV-2 infectivity MESHD, while inflammatory cytokines IL-6 HGNC, or G-CSF HGNC worsen COVID-19 MESHD severity. We show MEK HGNC inhibitors (MEKi) VS-6766, trametinib and selumetinib reduce ACE2 HGNC expression in human cells. Chloroquine or hydroxychloroquine increase cleaved active SP-domain of TMPRSS2 HGNC, and this is potentiated by MEKi. In some human cells, remdesivir increases ACE2 HGNC-promoter luciferase-reporter expression, ACE2 HGNC mRNA and protein, and ACE2 HGNC expression is attenuated by MEKi. We show elevated cytokines in COVID-19 MESHD- (+) patient plasma (N=9) versus control (N=11). TMPRSS2 HGNC, inflammatory cytokines G-CSF HGNC, M- CSF HGNC, IL-1a HGNC, IL-6 HGNC and MCP-1 HGNC are suppressed by MEKi alone or in combination with remdesivir. MEKi enhance NK cell (but not T-cell) killing of target-cells, without suppressing TRAIL HGNC-mediated cytotoxicity MESHD. We generated a pseudotyped SARS-CoV-2 virus with a lentiviral core but with the SARS-CoV-2 D614 or G614 SPIKE (S) protein PROTEIN on its envelope and used VSV-G lentivirus as a negative control. Our results show infection of human bronchial epithelial cells or lung cancer MESHD cells and that MEKi suppress infectivity of the SARS-CoV-2-S pseudovirus following infection MESHD. We show a drug class-effect with MEKi to promote immune responses involving NK cells, inhibit inflammatory cytokines and block host-factors for SARS-CoV-2 infection MESHD leading also to suppression of SARS-CoV-2-S pseudovirus infection MESHD of human cells in a model system. MEKi may attenuate coronavirus infection MESHD to allow immune responses and antiviral agents to control COVID-19 MESHD disease progression and severity.

    IL-33 HGNC expression in response to SARS-CoV-2 correlates with seropositivity in COVID-19 MESHD convalescent individuals

    Authors: Michal A Stanczak; David E Sanin; Petya Apostolova; Gabriele Nerz; Dimitrios Lampaki; Maike Hofmann; Daniel Steinmann; Robert Thimme; Gerhard Mittler; Cornelius F Waller; Edward J Pearce; Erika L Pearce

    doi:10.1101/2020.07.09.20148056 Date: 2020-07-10 Source: medRxiv

    Our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still developing. We investigated seroprevalence and immune responses in subjects professionally exposed to SARS-CoV-2 and their family members (155 individuals; ages 5-79 years). Seropositivity for SARS-CoV-2 spike PROTEIN glycoprotein aligned with PCR results that confirmed previous infection. Anti-spike IgG titers remained high 60 days post-infection and did not associate with symptoms, but spike-specific IgM did associate with malaise and fever MESHD. We found limited household transmission, with children of infected individuals seldomly seropositive, highlighting professional exposure as the dominant route of infection in our cohort. We analyzed PBMCs from a subset of seropositive and seronegative adults. TLR7 HGNC agonist- activation revealed an increased population of IL-6+TNF-IL-1 HGNC{beta}+ monocytes, while SARS-CoV-2 peptide stimulation elicited IL-33 HGNC, IL-6 HGNC, IFNa2 HGNC, and IL-23 HGNC expression in seropositive individuals. IL-33 HGNC correlated with CD4+ T cell activation in PBMCs from convalescent subjects, and was likely due to T cell-mediated effects on IL-33 HGNC- producing cells. IL-33 HGNC is associated with pulmonary infection MESHD and chronic diseases like asthma MESHD and COPD, but its role in COVID-19 MESHD is unknown. Analysis of published scRNAseq data of bronchoalveolar lavage fluid MESHD ( BALF MESHD) from patients with mild to severe COVID-19 MESHD revealed a population of IL-33 HGNC-producing cells that increases with disease. Together these findings show that IL-33 HGNC production is linked to SARS-CoV- 2 infection MESHD and warrant further investigation of IL-33 HGNC in COVID-19 MESHD pathogenesis and immunity.

    Type 2 and interferon inflammation strongly regulate SARS-CoV-2 related gene expression in the airway epithelium

    Authors: Satria P Sajuthi; Peter DeFord; Nathan D Jackson; Michael T Montgomery; Jamie L Everman; Cydney L Rios; Elmar Pruesse; James D Nolin; Elizabeth G Plender; Michael E Wechsler; Angel CY Mak; Celeste Eng; Sandra Salazar; Vivian Medina; Eric M Wohlford; Scott Huntsman; Deborah A Nickerson; Soren Germer; Michael C Zody; Goncalo Abecasis; Hyun Min Kang; Kenneth M Rice; Sam Oh; Jose Rodriguez-Santana; Esteban G Burchard; Max A Seibold

    doi:10.1101/2020.04.09.034454 Date: 2020-04-10 Source: bioRxiv

    Coronavirus disease 2019 MESHD ( COVID-19 MESHD) outcomes vary from asymptomatic infection to death. This disparity may reflect different airway levels of the SARS-CoV-2 receptor, ACE2 HGNC, and the spike protein PROTEIN activator, TMPRSS2 HGNC. Here we explore the role of genetics and co-expression networks in regulating these genes in the airway, through the analysis of nasal airway transcriptome data from 695 children. We identify expression quantitative trait loci (eQTL) for both ACE2 HGNC and TMPRSS2 HGNC, that vary in frequency across world populations. Importantly, we find TMPRSS2 HGNC is part of a mucus secretory network, highly upregulated by T2 inflammation MESHD through the action of interleukin-13 HGNC, and that interferon response to respiratory viruses highly upregulates ACE2 HGNC expression. Finally, we define airway responses to coronavirus infections MESHD in children, finding that these infections upregulate IL6 HGNC while also stimulating a more pronounced cytotoxic immune response relative to other respiratory viruses. Our results reveal mechanisms likely influencing SARS-CoV-2 infectivity MESHD and COVID-19 MESHD clinical outcomes.

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MeSH Disease
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SARS-CoV-2 Proteins


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