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HGNC Genes

SARS-CoV-2 proteins

NSP5 (1)

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    Drug repurposing to face Covid-19 MESHD: Celastrol, a potential leading drug capable of inhibiting SARS-CoV-2 replication and induced inflammation MESHD

    Authors: Carlos A. Fuzo; Ronaldo B. Martins; Thais F.C. Fraga-Silva; Martin K. Amstalden; Thais Canassa-DeLeo; Juliano P. Souza; Thais M. Lima; Lúcia H. Faccioli; Suzelei C. França; Vânia L.D. Bonato; Eurico A. Neto; Marcelo Dias-Baruffi

    doi:10.1101/2021.04.20.439992 Date: 2021-04-20 Source: bioRxiv

    The global emergence of Covid-19 MESHD has caused huge human casualties. Clinical manifestations of the disease vary from asymptomatic to lethal, and the symptomatic form can be associated with cytokine storm and non-homeostatic inflammatory response. In face of the urgent demand for effective drugs to treat Covid-19 MESHD, we have searched for candidate compounds using a drug repurposing approach based on in silico analysis followed by biological validation. Here we identified celastrol, a pentacyclic triterpene isolated from Tripterygium wilfordii Hook F - a plant used in traditional Chinese medicine - as one of the best compounds out of 39 repurposed drug candidates. Celastrol reverted gene expression signature from SARS-CoV-2-infected MESHD cells; bound with high-affinity energy to viral molecular targets such as main protease PROTEIN ( Mpro PROTEIN) and receptor-biding domain (RBD); inhibited SARS-CoV-2 replication in monkey (Vero and Vero-ACE2) and human (Caco-2 and Calu-3) cell lines; and decreased interleukin-6 HGNC ( IL-6 HGNC) secretion in SARS-CoV-2-infected MESHD human cell lines. Interestingly, celastrol acted in a concentration-dependent manner, with undetectable signs of cytotoxicity MESHD. Therefore, celastrol is a promising lead drug candidate to treat Covid-19 MESHD due to its ability to suppress SARS-CoV-2 replication and IL-6 HGNC production in infected cells, two critical events in the pathophysiology of this disease.

    Predicting the severity of disease progression in COVID-19 MESHD at the individual and population level: A mathematical model

    Authors: Narendra Chirmule; Pradio Nair; Bela Desai; Ravindra Khare; Vivek R Nerurkar; Amitabh Gaur

    doi:10.1101/2021.04.01.21254804 Date: 2021-04-07 Source: medRxiv

    The impact of COVID-19 MESHD disease on health and economy has been global, and the magnitude of devastation is unparalleled in modern history. Any potential course of action to manage this complex disease requires the systematic and efficient analysis of data that can delineate the underlying pathogenesis. We have developed a mathematical model of disease progression to predict the clinical outcome, utilizing a set of causal factors known to contribute to COVID-19 MESHD pathology such as age, comorbidities, and certain viral and immunological parameters. Viral load and selected indicators of a dysfunctional MESHD immune response, such as cytokines IL-6 HGNC and IFNab; which contribute to the cytokine storm and fever MESHD, parameters of inflammation MESHD d-dimer and ferritin, aberrations in lymphocyte number, lymphopenia MESHD, and neutralizing antibodies were included for the analysis. The model provides a framework to unravel the multi-factorial complexities of the immune response manifested in SARS-CoV-2 infected MESHD individuals. Further, this model can be valuable to predict clinical outcome at an individual level and to develop strategies for allocating appropriate resources to mitigate severe cases at a population level.

    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.

    Early immune pathology and persistent dysregulation MESHD characterise severe COVID-19 MESHD

    Authors: Laura Bergamaschi; Federica Mescia; Lorinda Turner; Aimee Hanson; Prasanti Kotagiri; Benjamin J. Dunmore; Helene Ruffieux; Aloka DeSa; Oisin Huhn; Mark R. Wills; Stephen Baker; Rainer Doffinger; Gordon Dougan; Anne Elmer; Ian G Goodfellow; Ravindra K. Gupta; Myra Hosmillo; Kelvin Hunter; Nathalie Kingston; Paul J. Lehner; Nicholas J. Matheson; Jeremy K. Nicholson; Anna M. Petrunkina; Sylvia Richardson; Caroline Saunders; James E.D. Thaventhiran; Erik J.M. Toonen; Michael P. Weekes; - CambridgeInstituteofTherapeuticImmunologyandInfectiousDisease-NationalInstituteofHealthResearch(CITI; Mark Toshner; Christoph Hess; John R. Bradley; Paul A. Lyons; Kenneth G.C. Smith

    doi:10.1101/2021.01.11.20248765 Date: 2021-01-15 Source: medRxiv

    In a study of 207 SARS-CoV2-infected MESHD individuals with a range of severities followed over 12 weeks from symptom onset, we demonstrate that an early robust immune response, without systemic inflammation MESHD, is characteristic of asymptomatic or mild disease. Those presenting to hospital had delayed adaptive responses and systemic inflammation MESHD already evident at around symptom onset. Such early evidence of inflammation MESHD suggests immunopathology may be inevitable in some individuals, or that preventative intervention might be needed before symptom onset. Viral load does not correlate with the development of this pathological response, but does with its subsequent severity. Immune recovery is complex, with profound persistent cellular abnormalities correlating with a change in the nature of the inflammatory response, where signatures characteristic of increased oxidative phosphorylation and reactive-oxygen species-associated inflammation MESHD replace those driven by TNF HGNC and IL-6 HGNC. These late immunometabolic inflammatory changes and unresolved immune cell defects, if persistent, may contribute to "long COVID".

    Cerebrospinal fluid in COVID-19 MESHD neurological complications: no cytokine storm or neuroinflammation.

    Authors: Maria A. Garcia; Paula V. Barreras; Allie Lewis; Gabriel Pinilla; Lori J. Sokoll; Thomas Kickler; Heba Mostafa; Mario Caturegli; Abhay Moghekar; Kathryn C. Fitzgerald; - Hopkins Neuro-COVID-19 Group; Carlos A Pardo

    doi:10.1101/2021.01.10.20249014 Date: 2021-01-12 Source: medRxiv

    BACKGROUND. Neurological complications MESHD occur in COVID-19 MESHD. We aimed to examine cerebrospinal fluid (CSF) of COVID-19 MESHD subjects with neurological complications MESHD and determine presence of neuroinflammatory changes implicated in pathogenesis. METHODS. Cross-sectional study of CSF neuroinflammatory profiles from 18 COVID-19 MESHD subjects with neurological complications categorized by diagnosis ( stroke MESHD, encephalopathy MESHD, headache MESHD) and illness severity (critical, severe, moderate, mild). COVID-19 MESHD CSF was compared with CSF from healthy, infectious and neuroinflammatory disorders MESHD and stroke MESHD controls (n=82). Cytokines ( IL-6 HGNC, TNF-alpha HGNC, IFN-gamma HGNC, IL-10 HGNC, IL-12p70, IL-17A HGNC), inflammation MESHD and coagulation markers (high-sensitivity- C Reactive Protein HGNC [hsCRP], ferritin, fibrinogen HGNC, D-dimer, Factor VIII) and neurofilament light chain ( NF-L HGNC), were quantified. SARS-CoV2 RNA and SARS-CoV2 IgG and IgA antibodies in CSF were tested with RT-PCR and ELISA. RESULTS. CSF from COVID-19 MESHD subjects showed a paucity of neuroinflammatory changes, absence of pleocytosis MESHD or specific increases in pro-inflammatory markers or cytokines ( IL-6 HGNC, ferritin, or D-dimer). Anti-SARS-CoV2 antibodies in CSF of COVID-19 MESHD subjects (77%) were observed despite no evidence of SARS-CoV2 viral RNA. A similar increase of pro-inflammatory cytokines ( IL-6 HGNC, TNF-alpha HGNC;, IL-12p70) and IL-10 HGNC in CSF of COVID-19 MESHD and non- COVID-19 MESHD stroke MESHD subjects was observed compared to controls. CSF-NF-L was elevated in subjects with stroke MESHD and critical COVID-19 MESHD. CSF-hsCRP was present almost exclusively in COVID-19 MESHD cases. CONCLUSION. The paucity of neuroinflammatory changes in CSF of COVID-19 MESHD subjects and lack of SARS-CoV2 RNA do not support the presumed neurovirulence of SARS-CoV2 or neuroinflammation MESHD in pathogenesis of neurological complications in COVID-19 MESHD. Elevated CSF-NF-L indicates neuroaxonal injury MESHD in COVID-19 MESHD cases. The role of CSF SARS-CoV2 IgG antibodies is still undetermined.

    Prognostic value of thrombin HGNC generation parameters in hospitalized COVID-19 MESHD patients 

    Authors: María Eugenia de la Morena-Barrio; Carlos Bravo-Pérez; Antonia Miñano; Belén de la Morena-Barrio; María Piedad Fernandez-Perez; Enrique Bernal; José Miguel Gómez-Verdu; María Teresa Herranz; Vicente Vicente; Javier Corral; María Luisa Lozano

    doi:10.21203/rs.3.rs-115220/v1 Date: 2020-11-24 Source: ResearchSquare

    Background. SARS-CoV-2 infection MESHD ARS-CoV-2 infection increases MESHDthe risk of t hrombosis MESHDby different mechanisms not fully characterized. Although still debated, an increase in D-dimer has been proposed as a first-line hemostasis test associated with t hromboembolic MESHDrisk and unfavorable prognosis. Objective. We aim to systematically and comprehensively evaluate the association between t hrombin HGNCgeneration parameters and the inflammatory and hypercoagulable state, as well as their prognostic value in COVID-19 MESHD patientsMethods. A total of 127 hospitalized patients with confirmed COVID-19 MESHD, 24 hospitalized patients with SARS-CoV-2-negative p neumonia MESHDand 12 healthy subjects were included. Clinical characteristics, t hrombin HGNCgeneration triggered by tissue factor with and without soluble thrombomodulin, and also by silica, as well as other biochemical parameters were assessed.Results. Despite the frequent use of heparin, COVID-19 MESHD patients had similar t hrombin HGNCgeneration than healthy controls. In COVID-19 MESHD patients, the t hrombin HGNCgeneration lag-time positively correlated with markers of cell lysis (LDH), i nflammation MESHD(CRP, I L-6) HGNC and coagulation (D-dimer), while the endogenous t hrombin HGNCpotential (ETP) inversely correlated with D-dimer and LDH, and positively correlated with f ibrinogen HGNClevels. Patients with more prolonged lag-time and decreased ETP presented with increased ISTH-DIC scores, and had more severe disease (vascular events and d eath) MESHD. The ROC curve and Kaplan Meier estimate indicated that the D-dimer/ETP ratio was associated with in-hospital mortality (HR 2.5; p=0.006), and with the occurrence of major adverse events (composite end-point of vascular events and d eath) MESHD (HR 2.38; p=0.004).Conclusions. The t hrombin HGNCgeneration ETP and lag-time variables correlate with thromboinflammatory markers, and the D-dimer/ETP ratio can predict major adverse events in COVID-19 MESHD.

    Broad SARS-CoV-2 cell tropism and immunopathology in lung tissues from fatal COVID-19 MESHD

    Authors: Suzane Ramos da Silva; Enguo Ju; Wen Meng; Alberto E. Paniz Mondolfi; Sanja Dacic; Anthony Green; Clare Bryce; Zachary Grimes; Mary E Fowkes; Emilia M. Sordillo; Carlos Cordon-Cardo; Haitao Guo; Shou-Jiang Gao

    doi:10.1101/2020.09.25.20195818 Date: 2020-09-29 Source: medRxiv

    Background Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection MESHD in patients with Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) prominently manifests with pulmonary symptoms histologically reflected by diffuse alveolar damage MESHD (DAD), excess inflammation MESHD, pneumocyte hyperplasia MESHD and proliferation, and formation of platelet aggregates or thromboemboli MESHD. However, the mechanisms mediating these processes remain unclear. Methods We performed multicolor staining for viral proteins, and lineage cell markers to identify SARS-CoV-2 tropism MESHD and to define the lung pathobiology in postmortem tissues from five patients with fatal SARS-CoV-2 infections MESHD SARS-CoV-2 infections MESHD. Findings The lung parenchyma showed severe DAD MESHD with thromboemboli MESHD in all cases. SARS-CoV-2 infection MESHD was found in an extensive range of cells including alveolar epithelial type II/pneumocyte type II MESHD (AT2) cells (HT2-280), ciliated cells (tyr--tubulin), goblet cells ( MUC5AC HGNC), club-like cells ( MUC5B HGNC) and endothelial cells ( CD31 HGNC and CD34 HGNC). Greater than 90% of infiltrating immune cells were positive for viral proteins including macrophages and monocytes ( CD68 HGNC and CD163 HGNC), neutrophils ( ELA-2 HGNC), natural killer (NK) cells ( CD56 HGNC), B-cells ( CD19 HGNC and CD20 HGNC), and T-cells (CD3{varepsilon}). Most but not all infected cells were positive for the viral entry receptor angiotensin-converting enzyme-2 HGNC ( ACE2 HGNC). The numbers of infected and ACE2 HGNC-positive cells correlated with the extent of tissue damage. The infected tissues exhibited low numbers of B-cells and abundant CD3{varepsilon}+ T-cells consisting of mainly T helper cells ( CD4 HGNC), few cytotoxic T cells (CTL, CD8 HGNC), and no T regulatory cell ( FOXP3 HGNC). Antigen presenting molecule HLA-DR of B and T cells was abundant in all cases. Robust interleukin-6 HGNC ( IL-6 HGNC) expression was present in most uninfected and infected cells, with higher expression levels observed in cases with more tissue damage. Interpretation In lung tissues from severely affected COVID-19 MESHD patients, there is evidence for broad SARS-CoV-2 cell tropisms, activation of immune cells, and clearance of immunosuppressive cells, which could contribute to severe tissue damage, thromboemboli, excess inflammation MESHD and compromised adaptive immune responses.

    Transcriptional Profiling of Leukocytes in Critically Ill COVID19 MESHD Patients: Implications for Interferon Response and Coagulation

    Authors: Sean E. Gill; Claudia C. dos Santos; David B. O’Gorman; David E. Carter; Eric K. Patterson; Marat Slessarev; Claudio Martin; Mark Daley; Michael R. Miller; Gediminas Cepinskas; Douglas D. Fraser

    doi:10.21203/rs.3.rs-63632/v2 Date: 2020-08-21 Source: ResearchSquare

    Background: COVID19 MESHD is caused by the SARS-CoV-2 virus MESHD and has been associated with severe inflammation MESHD leading to organ dysfunction and mortality. Our aim was to profile the transcriptome in leukocytes from critically ill patients positive for COVID19 MESHD compared to those negative for COVID19 MESHD to better understand the COVID19 MESHD associated host response. For these studies, all patients admitted to our tertiary care intensive care unit (ICU) suspected of being infected with SARS-CoV-2, using standardized hospital screening methodologies, had blood samples collected at the time of admission to the ICU. Transcriptome profiling of leukocytes via ribonucleic acid sequencing (RNAseq) was then performed and differentially expressed genes as well as significantly enriched gene sets were identified.Results: We enrolled seven COVID19 MESHD+ (PCR positive, 2 SARS-CoV-2 genes) and seven age- and sex-matched COVID19 MESHD- (PCR negative) control ICU patients. Cohorts were well-balanced with the exception that COVID19 MESHD- patients had significantly higher total white blood cell counts and circulating neutrophils and COVID19 MESHD+ patients were more likely to suffer bilateral pneumonia MESHD. The mortality rate for this cohort of COVID19 MESHD+ ICU patients was 29%. As indicated by both single-gene based and gene set (GSEA) approaches, the major disease-specific transcriptional responses of leukocytes in critically ill COVID19 MESHD+ ICU patients were: (i) a robust overrepresentation of interferon related gene expression; (ii) a marked decrease in the transcriptional level of genes contributing to general protein synthesis and bioenergy metabolism; and (iii) the dysregulated expression of genes associated with coagulation, platelet function, complement activation, and tumour necrosis factor MESHD/ interleukin 6 HGNC signalling.  Conclusions: Our findings demonstrate that critically ill COVID19 MESHD+ patients on day 1 of admission to the ICU display a unique leukocyte transcriptional profile that distinguishes them from COVID19 MESHD- patients, providing guidance for future targeted studies exploring novel prognostic and therapeutic aspects of COVID19 MESHD.

    Mapping Systemic Inflammation and Antibody Responses in Multisystem Inflammatory Syndrome in Children (MIS-C)

    Authors: Conor Gruber; Roosheel Patel; Rebecca Trachman; Lauren Lepow; Fatima Amanat; Florian Krammer; Karen M. Wilson; Kenan Onel; Daniel Geanon; Kevin Tuballes; Manishkumar Patel; Konstantinos Mouskas; Nicole Simons; Vanessa Barcessat; Diane Del Valle; Samantha Udondem; Gurpawan Kang; Sandeep Gangadharan; George Ofori-Amanfo; Adeeb Rahman; Seunghee Kim-Schulze; Alexander Charney; Sacha Gnjatic; Bruce Gelb; Miriam Merad; Dusan Bogunovic

    doi:10.1101/2020.07.04.20142752 Date: 2020-07-06 Source: medRxiv

    Initially, the global outbreak of COVID-19 MESHD caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spared children from severe disease. However, after the initial wave of infections, clusters of a novel hyperinflammatory disease MESHD have been reported in regions with ongoing SARS-CoV-2 MESHD epidemics. While the characteristic clinical features are becoming clear, the pathophysiology remains unknown. Herein, we report on the immune profiles of eight Multisystem Inflammatory Syndrome MESHD in Children ( MIS HGNC-C) cases. We document that all MIS HGNC-C patients had evidence of prior SARS-CoV-2 exposure, mounting an antibody response with normal isotype-switching and neutralization capability. We further profiled the secreted immune response by high-dimensional cytokine assays, which identified elevated signatures of inflammation MESHD ( IL-18 HGNC and IL-6 HGNC), lymphocytic and myeloid chemotaxis and activation ( CCL3 HGNC, CCL4 HGNC, and CDCP1 HGNC) and mucosal immune dysregulation ( IL-17A HGNC, CCL20 HGNC, CCL28 HGNC). Mass cytometry immunophenotyping of peripheral blood revealed reductions of mDC1 and non-classical monocytes, as well as both NK- and T- lymphocytes, suggesting extravasation to affected tissues. Markers of activated myeloid function were also evident, including upregulation of ICAM1 HGNC and FcR1 in neutrophil and non-classical monocytes, well-documented markers in autoinflammation MESHD and autoimmunity that indicate enhanced antigen presentation and Fc-mediated responses. Finally, to assess the role for autoimmunity secondary to infection, we profiled the auto-antigen reactivity of MIS HGNC-C plasma, which revealed both known disease-associated autoantibodies (anti-La) and novel candidates that recognize endothelial, gastrointestinal and immune-cell antigens. All patients were treated with anti- IL6R HGNC antibody or IVIG, which led to rapid disease resolution tracking with normalization of inflammatory markers.

    Treatment with Arbidol and Moxifloxacin in Ordinary and Severe Adult Patients Infected with COVID-19 MESHD

    Authors: DONGSHAN YU; SHUILIN SUN; YANHUA LI; WENNA XI; DI JIN; KE SUN; RONGYAN YU; XUEBING YAO; ZHIYING SONG; AOYU YANG; RUIXIA LUO; BIAOSHU ZOU; YUN LIU

    doi:10.1101/2020.05.30.20117598 Date: 2020-06-05 Source: medRxiv

    Background An outbreak of coronavirus disease 2019 MESHD ( COVID-19 MESHD) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely spread. We aim to investigate the therapeutic effect of arbidol and moxifloxacin in patients infected with SARS-CoV-2. Methods We collected and analyzed data on 94 patients with COVID-19 MESHD including 27 severe patients at the Intensive Care Unit (ICU) and 74 ordinary patients at general isolation ward in Wuhan Xiehe Hospital, from February 15, 2020 to March 15, 2020. All patients were treated with arbidol (100mg each time, three times a day for 14 days) and moxifloxacin (0.4g each time, once a day for 7-14 days). Other data was also collected including demographic data, symptoms, laboratory findings, treatments and clinical outcomes. Results In basic characteristics, compared with the ordinary patients, the severe patients were older (median age was 63.0 years V.S 57.0 years, p=0.03), had higher proportion of hypertension MESHD (30% V.S 9%, p=0.03), higher possibility of getting fatigue and/or myalgia MESHD (26% V.S 6%, p=0.03), and had more obvious dyspnea MESHD symptom (26% V.S 3%, p=0.006). In regarding to laboratory results, we found the severe patients have higher white blood cell counts (p=0.003), neutrophil counts (p=0.007), higher levels of D-dimer (p<0.001), ALT (p<0.001) and AST HGNC (p=0.013) than the ordinary patients. After treatment of arbidol and moxifloxacin for one week, the rates of SARS-CoV-2 nucleic acid turning negative were 69.2% in the severe group and 77.8% in the ordinary group. A peculiar phenomenon was that IL-6 HGNC stands out among the cytokines in both groups, and higher in severe group than the ordinary one (p=0.011). After treating with arbidol and moxifloxacin for one week, IL-6 HGNC decreased significantly in severe group (p=0.023). Conclusion In summary, we proved the treatment of arbidol and moxifloxacin could be helpful in reducing viral load and inflammation MESHD during SARS-CoV2 infection MESHD, especially for negatively regulating fatal inflammation MESHD in severe COVID-19 MESHD patients. However, more evidence awaits further clinical verification.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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