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HGNC Genes

SARS-CoV-2 proteins

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    A Meta-analysis of Comorbidities in COVID-19 MESHD: Which Diseases increase the Susceptibility of SARS-CoV-2 Infection MESHD?

    Authors: Srinivasan Ramachandran; Manoj Kumar Singh; Ahmed Mobeen; Amit Chandra; Sweta Joshi

    id:10.20944/preprints202009.0486.v1 Date: 2020-09-21 Source: Preprints.org

    Background: Comorbidities have been frequently reported in COVID-19 MESHD patients, which often lead to more severe outcomes. The underlying molecular mechanisms behind these clinical observations have not yet been explained. Herein, we investigated the disease-specific gene expression signatures that may induce susceptibility to SARS-CoV-2 infection MESHD. Methods: We studied 30 frequently occurring acute, chronic, or infectious diseases of recent times that have shown comorbidity in one or another respiratory disease MESHD(s) caused by pathogenic human infecting coronaviruses, especially SARS-CoV-2. We retrieved array-based gene expression data for each disease and control from relevant datasets. Subsequently, all the datasets were quantile normalized, and log-2 transformed data was used for analysis. Results The expression of ACE2 HGNC receptor and host proteases, namely FURIN HGNC and TMPRSS2 HGNC that are essential for cellular entry of SARS-CoV-2, was upregulated in all six studied subtypes of leukemia MESHD (hereafter, referred as leukemia MESHD). The expression of ACE2 HGNC was also increased in psoriasis MESHD, lung cancer MESHD, Non-alcoholic fatty liver disease MESHD ( NAFLD MESHD), breast cancer MESHD, and pulmonary arterial hypertension MESHD patients. The expression of FURIN HGNC was higher in psoriasis MESHD, NAFLD MESHD, lung cancer MESHD, and in type II diabetic liver MESHD, whereas it was lowered in breast cancer MESHD. Similarly, the expression of TMPRSS2 HGNC was increased during lung cancer MESHD and type II diabetes MESHD; it was decreased during psoriasis MESHD, NAFLD MESHD, lung cancer MESHD, breast cancer MESHD, and cervical cancer MESHD.Furthermore, a heightened expression of genes that are involved in immune response was observed in leukemia MESHD patients, as shown by the higher expression of IFNA2 HGNC, IFNA8 HGNC, IFNA10 HGNC, IFNA14 HGNC, IFNA16 HGNC, IFNA21 HGNC, IFNB1 HGNC, CXCL10 HGNC, and IL6 HGNC. The expression of JAK1 HGNC, STAT1 HGNC, IL6 HGNC, and CXCL10 HGNC was higher in NAFLD MESHD. Besides, JAK1 HGNC and STAT1 HGNC were upregulated in type II diabetic muscles MESHD. In addition, most of the upregulated genes in COVID-19 MESHD patients showed a similar trend in leukemia MESHD, NAFLD MESHD, and psoriasis MESHD. Furthermore, SARS-CoV-2, SARS-CoV MESHD and MERS CoV, were found to commonly alter two genes, namely, CARBONIC ANHYDRASE 11 and CLUSTERIN.Conclusions: The genes that may confer susceptibility to SARS-CoV-2 infection MESHD are mostly upregulated in leukemia MESHD patients; hence, leukemia MESHD patients are relatively more susceptible to develop COVID-19 MESHD, followed by other chronic disorders MESHD, such as, NAFLD MESHD, type II diabetes MESHD, psoriasis MESHD, and hypertension MESHD. This study identifies key genes that are altered in the studied diseases types, which may aid in the infection of SARS-CoV-2 MESHD and underlie COVID-19 MESHD associated comorbidities.

    SARS-CoV2 drives JAK1 HGNC/2-dependent local and systemic complement hyper-activation

    Authors: Bingyu Yan; Tilo Freiwald; Daniel Chauss; Luopin Wang; Erin West; Jack Bibby; Matthew Olson; Shahram Kordasti; Didier Portilla; Arian Laurence; Michail S Lionakis; Claudia Kemper; Behdad Afzali; Majid Kazemian

    doi:10.21203/rs.3.rs-33390/v1 Date: 2020-06-05 Source: ResearchSquare

    Patients with coronavirus disease 2019 MESHD ( COVID-19 MESHD) present with a range of devastating acute clinical manifestations affecting the lungs, liver, kidneys and gut. The best-characterized entry receptor for the disease-causing virus SARS-CoV2, angiotensin converting enzyme (ACE) 2 HGNC, is highly expressed in these tissues. However, the pathways that underlie the disease are still poorly understood. Here we show that the complement system is unexpectedly one of the intracellular pathways most highly induced by SARS-CoV2 infection MESHD in lung epithelial and liver cells. Within cells of the bronchoalveolar lavage of patients, distinct signatures of complement activation in myeloid, lymphoid and epithelial cells tracked with disease severity. Modelling the regulome of host genes induced by COVID-19 MESHD and the drugs that could normalize these genes both implicated the JAK1 HGNC/2- STAT1 HGNC signaling system downstream of type I interferon receptors, and NF-kB. Ruxolitinib, a JAK1/2 inhibitor and the top predicted pharmaceutical candidate, normalized interferon signature genes, IL-6 HGNC (the best characterized severity marker in COVID-19 MESHD) and all complement genes induced by SARS-CoV2, but did not affect NF-kB-regulated genes. We predict that combination therapy with JAK inhibitors and other agents with the potential to normalize NF-kB-signaling, such as anti-viral agents, may serve as an effective clinical strategy. 

    JAK1 HGNC inhibition blocks lethal sterile immune responses:implications for COVID-19 MESHD therapy

    Authors: Kathryn Tuttle; Ross Minter; Katherine Waugh; Paula Araya; Michael Ludwig; Colin Sempeck; Keith Smith; Zdenek Andrysik; Matthew Burchill; Beth Tamburini; David Orlicky; Kelly D Sullivan; Joaquin Espinosa

    doi:10.1101/2020.04.07.024455 Date: 2020-04-09 Source: bioRxiv

    Cytokine storms are drivers of pathology and mortality in myriad viral infections affecting the human population. In SARS-CoV-2-infected MESHD patients, the strength of the cytokine storm has been associated with increased risk of acute respiratory distress syndrome MESHD, myocardial damage MESHD, and death MESHD. However, the therapeutic value of attenuating the cytokine storm in COVID-19 MESHD remains to be defined. Here, we report results obtained using a novel mouse model of lethal sterile anti-viral immune responses. Using a mouse model of Down syndrome ( DS MESHD) with a segmental duplication of a genomic region encoding four of the six interferon receptor genes (Ifnrs), we demonstrate that these animals overexpress Ifnrs and are hypersensitive to IFN stimulation. When challenged with viral mimetics that activate Toll-like receptor signaling and IFN anti-viral responses, these animals overproduce key cytokines, show exacerbated liver pathology, rapidly lose weight, and die. Importantly, the lethal immune hypersensitivity MESHD, accompanying cytokine storm, and liver hyperinflammation MESHD are blocked by treatment with a JAK1-specific inhibitor. Therefore, these results point to JAK1 inhibition as a potential strategy for attenuating the cytokine storm and consequent organ failure during overdrive immune responses. Additionally, these results indicate that people with DS, who carry an extra copy of the IFNR HGNC gene cluster encoded on chromosome 21, should be considered at high risk during the COVID-19 pandemic MESHD. One Sentence SummaryInhibition of the JAK1 kinase prevents pathology and mortality caused by a rampant innate immune response in mice.

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MeSH Disease
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SARS-CoV-2 Proteins


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