Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (15)

ProteinS1 (2)

ProteinN (1)


SARS-CoV-2 Proteins
    displaying 1 - 10 records in total 15
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    SARS-CoV-2 spike PROTEIN protein induces inflammation MESHD via TLR2 HGNC-dependent activation of the NF-κB pathway

    Authors: Shahanshah Khan; Mahnoush S. Shafiei; Christopher Longoria; John Schoggins; Rashmin C. Savani; Hasan Zaki

    doi:10.1101/2021.03.16.435700 Date: 2021-03-17 Source: bioRxiv

    Pathogenesis of COVID-19 MESHD is associated with a hyperinflammatory response; however, the precise mechanism of SARS-CoV-2-induced inflammation MESHD is poorly understood. Here we investigated direct inflammatory functions of major structural proteins of SARS-CoV-2. We observed that spike (S) protein PROTEIN potently induces inflammatory cytokines and chemokines including IL-6 HGNC, IL-1b HGNC, TNFa HGNC, CXCL1 HGNC, CXCL2 HGNC, and CCL2 HGNC, but not IFNs in human and mouse macrophages. No such inflammatory response was observed in response to membrane (M), envelope (E), and neucleocapsid ( N) proteins PROTEIN. When stimulated with extracellular S protein PROTEIN, human lung epithelial cells A549 also produce inflammatory cytokines and chemokines. Interestingly, epithelial cells expressing S protein PROTEIN intracellularly are non-inflammatory, but elicit an inflammatory response in macrophages when co-cultured. Biochemical studies revealed that S protein PROTEIN triggers inflammation MESHD via activation of the NF-kB pathway in a MyD88 HGNC-dependent manner. Further, such an activation of the NF-kB pathway is abrogated in Tlr2 HGNC-deficient macrophages. Consistently, administration of S protein PROTEIN induces IL-6, TNF-a, and IL-1b in wild-type, but not Tlr2-deficient mice. Together these data reveal a mechanism for the cytokine storm during SARS-CoV-2 infection MESHD and suggest that TLR2 could be a potential therapeutic target for COVID-19 MESHD.

    A proteome-wide genetic investigation identifies several SARS-CoV-2-exploited host targets of clinical relevance

    Authors: Mohd Anisul Karim; Jarrod Shilts; Jeremy Schwartzentruber; James Hayhurst; Annalisa Buniello; Elmutaz Shaikho Elhaj Mohammed; Jie Zheng; Michael V. Holmes; David Ochoa; Miguel Carmona; Joseph Maranville; Tom R. Gaunt; Valur Emilsson; Vilmundur Gudnason; Ellen M. McDonagh; Gavin J. Wright; Maya Ghoussaini; Ian Dunham

    doi:10.1101/2021.03.15.21253625 Date: 2021-03-17 Source: medRxiv

    The virus SARS-CoV-2 can exploit biological vulnerabilities in susceptible hosts that predispose to development of severe COVID-19 MESHD. Previous reports have identified several host proteins related to the interferon response (e.g. OAS1 HGNC), interleukin-6 HGNC signalling ( IL-6R HGNC), and the coagulation cascade (linked via ABO HGNC) that were associated with risk of COVID-19 MESHD. In the present study, we performed proteome-wide genetic colocalisation tests leveraging publicly available protein and COVID-19 MESHD datasets, to identify additional proteins that may contribute to COVID-19 MESHD risk. Our analytic approach identified several known targets (e.g. ABO HGNC, OAS1 HGNC), but also nominated new proteins such as soluble FAS (colocalisation probability > 0.9, p = 1 x 10-4), implicating FAS-mediated apoptosis as a potential target for COVID-19 MESHD risk. We also undertook polygenic (pan) and cis-Mendelian randomisation analyses that showed consistent associations of genetically predicted ABO HGNC protein with several COVID-19 MESHD phenotypes. The ABO HGNC signal was associated with plasma concentrations of several proteins, with the strongest association observed with CD209 HGNC in several proteomic datasets. We demonstrated experimentally that CD209 HGNC directly interacts with the spike protein PROTEIN of SARS-CoV-2, suggesting a mechanism that could explain the ABO HGNC association with COVID-19 MESHD. Our work provides a prioritised list of host targets potentially exploited by SARS-CoV-2 and is a precursor for further research on CD209 HGNC and FAS as therapeutically tractable targets for COVID-19 MESHD.

    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.

    Humoral and cell-mediated response in colostrum after exposure to severe acute respiratory syndrome coronavirus 2 MESHD

    Authors: Vignesh Narayanaswamy; Brian Pentecost; Dominique Alfandari; Emily Chin; Kathleen Minor; Alyssa Kastrinakis; Tanya Lieberman; Kathleen F Arcaro; Heidi Leftwich

    doi:10.1101/2021.01.03.20248715 Date: 2021-01-04 Source: medRxiv

    BackgroundColostrum provides an immune sharing between a mother and her infant. The transfer in colostrum of antibodies against SARS-CoV-2 and the elicited cytokines may provide crucial protection to the infant. There is limited literature on the immune response to SARS-CoV-2 present in colostrum. ObjectiveTo evaluate the presence of antibodies specific to SARS-CoV-2 and the associated cytokines in colostrum from women who tested positive for the virus. Study DesignBetween March and September 2020 we obtained bilateral colostrum samples collected on spot cards within 48 hours of delivery from 15 new mothers who had previously tested positive for SARS-CoV-2. Five of these 15 COVID-19 MESHD positive women also provided bilateral liquid colostrum within 1-2 days of providing the spot card samples. Archived bilateral colostrum samples collected from 8 women during 2011-2013 were used as pre- COVID-19 MESHD controls. All samples were tested for reactivity to the Receptor Binding Domain (RBD) of the SARS-CoV-2 spike PROTEIN protein using an ELISA that measures SARS-CoV-2 RBD-specific IgA, IgG, and IgM, and for concentrations of 10 inflammatory cytokines ( IFN{gamma HGNC}, TNF HGNC, IL-1{beta HGNC}, IL-2 HGNC, IL-4 HGNC, IL-6 HGNC, IL-8 HGNC, IL-10 HGNC, IL-12, IL-13 HGNC) using a multiplex electrochemiluminescent sandwich assay. ResultsBilateral colostrum samples from 73%, 73% and 33% of the 15 COVID-19 MESHD mothers exhibited IgA, IgG, and IgM reactivity to RBD respectively. Colostrum samples from two of the 8 pre-pandemic controls showed IgA and IgG reactivity to RBD. Additionally, COVID-19 MESHD mothers had significantly higher levels of 9 of the 10 inflammatory markers (all except IFN{gamma HGNC}) as compared to the pre- COVID-19 MESHD controls. Comparable results were obtained with both the spot card-eluates and liquid samples. ConclusionsA strong humoral immune response is present in the colostrum of women who were infected with SARS-CoV-2 before delivering. High levels of 9 inflammatory markers were also present in the colostrum. The evolution and duration of the antibody response, as well as dynamics of the cytokine response, remain to be determined. Our results also indicate that future large-scale studies can be conducted with milk easily collected on paper spot cards.

    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.


    Authors: arif malik; Saima Iqbal; Sulayman Waquar; Muhammad Mansoor Hafeez

    doi:10.1101/2020.10.28.20221408 Date: 2020-11-03 Source: medRxiv

    INTRODUCTION: Outbreak of the novel COVID-19 MESHD infection identifies both causative agents that threaten global pandemic in 2003 and 2011. It is an enveloped virus with spike (S) protein PROTEIN attached that facilitates its receptor binding on the surface. Although it has brought about the global interest for the researchers and medical practitioner in the identification of potential targets that may be addressed in order to cope up with the situation. In the current study potential role of cytokines and related inflammatory markers have been identified that interplays in the progression of disease in COVID-19 MESHD patients. MATERIALS AND METHODS: Current study substitutes hundred and fifty (n=150) patients with novel- COVID-19 MESHD and hundred (n=100) healthy controls. After getting informed consent serum samples of the participants were collected and analyzed for their significance in the disease progression. Levels of Interleukins i.e., ( IL-1 HGNC,6,8,10,11) and tumor MESHD tumor HGNC necrosis MESHD factor-alpha ( TNF HGNC-) were determined with help of their specific spectrophotometric and ELISA methods. RESULTS: Findings of study show significant increase in the levels of interleukins and TNF HGNC- that signifies the presence of cytokine storm in worsening the condition in respect to the exposure of COVID-19 MESHD. Levels of IL-1 and 6 were significantly higher in patients (98.69 pg/ml and 71.95 pg/ml) as compared to controls (30.06 pg/ml and 9.46 pg/ml) where, (p=0.001 and 0.007). It also suggests that IL-6 HGNC is most sensitive test with about (98%) sensitivity in comparison with 96%,95%, 95%,93% and 92% in case of IL-10,1,8,11 and TNF-a HGNC respectively. CONCLUSION: Current study elucidate the effects of cytokines and respective inflammatory markers in the progression of the COVID-19 MESHD. Findings show that activation of macrophages and neutrophils have significant role in the worsening of the symptoms and progression of the viral infection MESHD. Thus, use of certain blockers in initial stages could serve with potent benefits in coping up the infectious condition.

    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.

    SARS-CoV-2 antibodies, serum inflammatory biomarkers and clinical severity of hospitalized COVID-19 MESHD Patients

    Authors: Roberto Gozalbo-Rovira; Estela Gimenez; Victor Latorre; Clara Frances-Gomez; Eliseo Albert; Javier Buesa; Alberto Marina; Maria Luisa Blasco; Jaime Signes-Costa; Jesus Rodriguez-Diaz; Ron Geller; David Navarro

    doi:10.1101/2020.07.22.20159673 Date: 2020-07-24 Source: medRxiv

    Background: The involvement of SARS-CoV-2 antibodies in mediating immunopathogenetic events in COVID-19 MESHD patients has been suggested. By using several experimental approaches, we investigated the potential association between SARS-CoV-2 IgGs recognizing the spike (S) protein PROTEIN receptor-binding domain (RBD), neutralizing antibodies (NtAb) targeting S, and COVID-19 MESHD severity. Patients and Methods: This unicenter, retrospective, observational study included 51 hospitalized patients (24 at the intensive care unit; ICU). A total of 93 sera from these patients collected at different time points from the onset of symptoms were analyzed. SARS-CoV-2 RBD IgGs were quantitated by ELISA and NtAb50 titers were measured in a GFP reporter-based pseudotyped virus platform. Demographic and clinical data, complete blood counts, as well as serum levels of ferritin, Dimer-D, C reactive protein HGNC ( CRP HGNC), lactose dehydrogenase (LDH), and interleukin-6 HGNC ( IL-6 HGNC) were retrieved from clinical charts. Results: The overall correlation between levels of both antibody measurements was good (Rho=0.79; P=0<0.001). SARS-CoV-2 RBD IgG and NtAb50 levels in sera collected up to day 30 after the onset of symptoms were comparable between ICU and non-ICU patients (P=>0.1). The percentage of patients who exhibited high NtAb50 titers ([≥]160) was similar (P=0.20) in ICU (79%) and non-ICU (60%) patients. Four ICU patients died; two of these achieved NtAb50 titers [≥]1/160 while the other two exhibited a 1/80 titer. Very weak (Rho=>0.0-<0.2) or weak (Rho=>0.2-<0.4) correlations were observed between anti-RBD IgGs, NtAb50, and serum levels pro-inflammatory biomarkers. Conclusions: The data presented herein do not support an association between SARS-CoV-2 RBD IgG or NtAb50 levels and COVID-19 MESHD severity

    A human disease model of SARS-CoV-2-induced lung injury and immune responses with a microengineered organ chip

    Authors: Min Zhang; Peng Wang; Ronghua Luo; Yaqing Wang; Zhongyu Li; Yaqiong Guo; Yulin Yao; Minghua Li; Tingting Tao; Wenwen Chen; Jianbao Han; Haitao Liu; Kangli Cui; Xu Zhang; Yongtang Zheng; Jianhua Qin

    doi:10.1101/2020.07.20.211789 Date: 2020-07-20 Source: bioRxiv

    Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that seriously endangers human health. There is an urgent need to build physiological relevant human models for deep understanding the complex organ-level disease processes and facilitating effective therapeutics for COVID-19 MESHD. Here, we first report the use of microengineered alveolus chip to create a human disease model of lung injury MESHD and immune responses induced by native SARS-CoV-2 at organ-level. This biomimetic system is able to reconstitute the key features of human alveolar MESHD-capillary barrier by co-culture of alveolar epithelial MESHD and microvascular endothelial cells under microfluidic flow. The epithelial cells on chip showed higher susceptibility to SARS-CoV-2 infection MESHD than endothelial cells identified by viral spike protein PROTEIN expression. Transcriptional analysis showed distinct responses of two cell types to SARS-CoV-2 infection MESHD, including activated type I interferon (IFN-I) signaling pathway in epithelium and activated JAK-STAT signaling pathway in endothelium. Notably, in the presence of circulating immune cells, a series of alveolar MESHD pathological changes were observed, including the detachment of endothelial cells, recruitment of immune cells, and increased production of inflammatory cytokines ( IL-6 HGNC, IL-8 HGNC, IL-1{beta} and TNF-). These new findings revealed a crucial role of immune cells in mediating lung injury MESHD and exacerbated inflammation MESHD. Treatment with antiviral compound remdesivir could suppress viral copy and alleviate the disruption of alveolar MESHD barrier integrity induced by viral infection MESHD. This bioengineered human organ chip system can closely mirror human-relevant lung pathogenesis and immune responses to SARS-CoV-2 infection MESHD, not possible by other in vitro models, which provides a promising and alternative platform for COVID-19 MESHD research and preclinical trials.

    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.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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