Corpus overview


Overview

MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (2)


Filter

Genes
Diseases
SARS-CoV-2 Proteins
    displaying 1 - 9 records in total 9
    records per page




    Soluble angiotensin-converting enzyme 2 HGNC is transiently elevated in COVID-19 MESHD and correlates with specific inflammatory and endothelial markers

    Authors: Annika Lundstrom; Louise Ziegler; Sebastian Havervall; Ann-Sofie Rudberg; Fien Von Meijenfeldt; Ton Lisman; Nigel Mackman; Per Sanden; Charlotte Thalin

    doi:10.1101/2021.03.03.21252841 Date: 2021-03-05 Source: medRxiv

    RationaleAngiotensin-converting enzyme 2 ( ACE2 HGNC) is the main entry receptor of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), but how SARS-CoV-2 interactions with ACE2 HGNC influences the renin-angiotensin system (RAS) in Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is unknown. ObjectiveTo measure circulating ACE2 HGNC and ACE HGNC levels in COVID-19 MESHD patients and investigate association with risk factors, outcome and inflammatory markers. Methods and resultsSoluble ACE2 HGNC (sACE2) and sACE concentrations were measured by ELISA in plasma samples from 114 hospital-treated COVID-19 MESHD patients and 10 healthy controls. Follow-up samples after four months were available for 58/114 patients. Von Willebrand MESHD Von Willebrand HGNC factor ( VWF HGNC), factor VIII ( fVIII HGNC), D-dimer, interleukin 6 ( IL-6 HGNC), tumor necrosis MESHD factor and plasminogen activator inhibitor 1 ( PAI-1 HGNC) had previously been determined. Levels of sACE2 were higher in COVID-19 MESHD patients than in healthy controls, median 5.0 (interquartile range 2.8-11.8) ng/ml versus 1.4 (1.1-1.6) ng/ml, p < 0.0001. sACE2 was higher in men than women, but were not affected by other risk factors for severe COVID-19 MESHD. sACE 2 decreased to 2.3 (1.6-3.9) ng/ml at follow-up, p < 0.0001, but remained higher than in healthy controls, p=0.012. Follow-up sACE2 levels were higher with increasing age, BMI, total number of comorbidities, for patients with diabetes MESHD and patients on RAS-inhibition. sACE was marginally lower during COVID-19 MESHD compared with at follow-up, 57 (45-70) ng/ml versus 72 (52-87) ng/ml, p=0.008. Levels of sACE2 and sACE did not differ depending on survival or disease severity (care level, respiratory support). sACE2 during COVID-19 MESHD correlated with VWF HGNC, fVIII HGNC and D-dimer, while sACE correlated with IL-6 HGNC, TNF HGNC and PAI-1 HGNC. ConclusionssACE2 was transiently elevated in COVID-19 MESHD, likely due to increased shedding from infected cells. sACE2 and sACE during COVID-19 MESHD differed distinctly in their correlations with markers of inflammation MESHD and endothelial dysfunction, suggesting release from different cell types and/or vascular beds.

    Neural epidermal growth factor-like 1 HGNC protein variant increases survival and modulates the inflammatory and immune responses in human ACE-2 HGNC transgenic mice infected with SARS-CoV-2

    Authors: Roopa Biswas; Shannon Eaker; Dharmendra Kumar Soni; Swagata Kar; Denae LoBato; Cymbeline Culiat

    doi:10.1101/2021.02.08.430254 Date: 2021-02-08 Source: bioRxiv

    Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) and is a worsening global pandemic. COVID-19 MESHD has caused at least 1.7 million deaths worldwide and over 300,000 in the United States. Recently, two promising vaccines are being administered in several countries. However, there remains an urgent need for a therapeutic treatment for COVID-19 MESHD patients with severe respiratory damage MESHD that can lead to intensive care, prolonged hospitalization, or mortality. Moreover, an increasing population of patients manifest lingering disabling symptoms (called Long Haulers). Here, we tested the efficacy of a recombinant neural epidermal growth factor like 1 protein variant (NELL1-NV1) in a COVID-19 MESHD mouse model, transgenic mice expressing the human angiotensin I-converting enzyme 2 HGNC ( ACE2 HGNC) receptor (tg-mice hACE2 HGNC) infected with SARS-CoV-2. The administration of NELL1-NV1 to SARS-CoV-2-infected MESHD tg-mice hACE2 HGNC significantly improved clinical health score and increased survival. Analyses of bronchoalveolar (BAL) fluid demonstrated decreased levels of several cytokines and chemokines (IFN-{gamma}, IL-10, IL-12 p70, CXCL-10/IP-10, MIG and Rantes), in NV1-treated treated mice compared to controls. Cytokines including IL-1 HGNC, IL-9 HGNC, IL-6 HGNC, LIX/ CXCL5 HGNC, KC/ CXCL1 HGNC, MIP-2 HGNC/ CXCL2 HGNC, MIP-1 HGNC/ CCL3 HGNC, and G-CSF HGNC, critical to immune responses such as neutrophil recruitment, viral clearance and vascularization, were increased compared to controls. Our data suggest the potential of NELL1 HGNC-NV1-based therapy to mitigate the cytokine storm, modulate the abnormal immune response and repair respiratory tissue damage in COVID-19 MESHD patients.

    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.

    Epigenetic Evolution of ACE2 HGNC and IL-6 HGNC Genes as Non-Canonical Interferon-Stimulated Genes Correlate to COVID-19 MESHD Susceptibility in Vertebrates

    Authors: Eric R. Sang; Yun Tian; Yuanying Gong; Laura C Miller; Yongming Sang

    doi:10.1101/2020.09.09.273268 Date: 2020-09-10 Source: bioRxiv

    Current novel coronavirus disease MESHD ( COVID-19 MESHD) has spread globally within a matter of months. The virus establishes a success in balancing its deadliness and contagiousness, and causes substantial differences in susceptibility and disease progression in people of different ages, genders and pre-existing comorbidities. Since these host factors are subjected to epigenetic regulation, relevant analyses on some key genes underlying COVID-19 MESHD pathogenesis were performed to longitudinally decipher their epigenetic correlation to COVID-19 MESHD susceptibility. The genes of host angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC, as the major virus receptor) and interleukin (IL)-6 (a key immune-pathological factor triggering cytokine storm) were shown to evince active epigenetic evolution via histone modification and cis/trans-factors interaction across different vertebrate species. Extensive analyses revealed that ACE2 HGNC ad IL-6 HGNC genes are among a subset of non-canonical interferon-stimulated genes (non-ISGs), which have been designated recently for their unconventional responses to interferons (IFNs) and inflammatory stimuli through an epigenetic cascade. Furthermore, significantly higher positive histone modification markers and position weight matrix (PWM) scores of key cis-elements corresponding to inflammatory and IFN signaling, were discovered in both ACE2 HGNC and IL6 HGNC gene promoters across representative COVID-19 MESHD-susceptible species compared to unsusceptible ones. Findings characterize ACE2 HGNC and IL-6 HGNC genes as non-ISGs that respond differently to inflammatory and IFN signaling from the canonical ISGs and their epigenetic properties may serve as biomarkers to longitudinally predict COVID-19 MESHD susceptibility in vertebrates and partially explain COVID-19 MESHD inequality in people of different subgroups.

    Modeling COVID-19 MESHD with Human Pluripotent Stem Cell-Derived Cells Reveals Synergistic Effects of Anti-inflammatory Macrophages with ACE2 HGNC Inhibition Against SARS-CoV-2

    Authors: Fuyu Duan; Liyan Guo; Liuliu Yang; Yuling Han; Abhimanyu Thakur; Benjamin E. Nilsson-Payant; Pengfei Wang; Zhao Zhang; Chui Yan Ma; Xiaoya Zhou; Teng Han; Tuo Zhang; Xing Wang; Dong Xu; Xiaohua Duan; Jenny Xiang; Hung-fat Tse; Can Liao; Weiren Luo; Fang-Ping Huang; Ya-Wen Chen; Todd Evans; Robert E. Schwartz; Benjamin tenOever; David D. Ho; Shuibing Chen; Jie Na; Qizhou Lian; Huanhuan Joyce Chen

    doi:10.21203/rs.3.rs-62758/v2 Date: 2020-08-20 Source: ResearchSquare

    Dysfunctional immune responses contribute critically to the progression of Coronavirus Disease MESHD-2019 ( COVID-19 MESHD) from mild to severe stages including fatality, with pro-inflammatory macrophages as one of the main mediators of lung hyper-inflammation MESHD. Therefore, there is an urgent need to better understand the interactions among SARS-CoV-2 permissive cells, macrophage, and the SARS-CoV-2 virus, thereby offering important insights into new therapeutic strategies.  Here, we used directed differentiation of human pluripotent stem cells (hPSCs) to establish a lung and macrophage co-culture system and model the host-pathogen interaction and immune response caused by SARS-CoV-2 infection MESHD. Among the hPSC-derived lung cells, alveolar type II MESHD and ciliated cells are the major cell populations expressing the viral receptor ACE2 HGNC and co-effector TMPRSS2 HGNC, and both were highly permissive to viral infection MESHD. We found that alternatively polarized macrophages (M2) and classically polarized macrophages (M1) had similar inhibitory effects on SARS-CoV-2 infection MESHD. However, only M1 macrophages significantly up-regulated inflammatory factors including IL-6 HGNC and IL-18 HGNC, inhibiting growth and enhancing apoptosis of lung cells. Inhibiting viral entry into target cells using an ACE2 HGNC blocking antibody enhanced the activity of M2 macrophages, resulting in nearly complete clearance of virus and protection of lung cells. These results suggest a potential therapeutic strategy, in that by blocking viral entrance to target cells while boosting anti-inflammatory action of macrophages at an early stage of infection, M2 macrophages can eliminate SARS-CoV-2, while sparing lung cells and suppressing the dysfunctional hyper MESHD-inflammatory response mediated by M1 macrophages.    

    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.

    Angiotensin-converting enzyme 2 HGNC, a SARS-CoV-2 receptor, is upregulated by interleukin-6 HGNC via STAT3 HGNC signaling in rheumatoid synovium

    Authors: Sho Mokuda; Tadahiro Tokunaga; Junya Masumoto; Eiji Sugiyama

    doi:10.1101/2020.05.26.115261 Date: 2020-05-27 Source: bioRxiv

    Detected in December 2019, the coronavirus disease 2019 MESHD ( COVID-19 MESHD) has since spread all over the world, resulting in a global pandemic. The disease is caused by severe acute respiratory syndrome-coronavirus-2 MESHD (SARS-CoV-2), and its symptoms usually include cough, fever MESHD, and gastrointestinal problems MESHD. Although the prevalence of rheumatoid arthritis MESHD ( RA MESHD) is about 1 % of the global population and RA MESHD patients naturally have a chance of acquiring COVID-19 MESHD in this pandemic, no studies have considered the expression of angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC) (a receptor for SARS-CoV-2) in synovial tissues. Our presenting data revealed that ACE2 HGNC expression was elevated in active rheumatoid MESHD synovium, and siRNA against STAT3 HGNC was able to downregulate ACE2 HGNC expression, which was in turn induced by IL-6 HGNC signaling.

    A blood-based comprehensive and systems-level analysis of disease stages, immune regulation and symptoms in COVID-19 MESHD patients

    Authors: Anguraj Sadanandam; Tobias Bopp; Santosh Dixit; David JHF Knapp; Chitra Priya Emperumal; Krishnaraj Rajalingam; Alan Melcher; Nagarajan Kannan

    doi:10.21203/rs.3.rs-30473/v1 Date: 2020-05-20 Source: ResearchSquare

    COVID-19 MESHD patients show significant clinical heterogeneity in presentation and outcomes that makes pandemic control and strategy difficult; optimising management requires a systems biology approach of understanding the disease. Here we sought to understand and infer complex system-wide changes in patients infected with coronaviruses ( SARS-CoV and SARS-CoV-2 MESHD; n=38 and 57 samples) at two different disease stages compared with healthy individuals (n=16) and patients with other infections (n=144). We applied inferential statistics/machine-learning approaches (the COVID-engine platform) to RNA profiles derived from peripheral blood mononuclear cells (PBMCs). Compared to healthy individuals, an integrated blood-based gene signatures distinguished acute-like (mimicking coronavirus-infected MESHD patients with prolonged hospitalisation) from recovering-like patients. These signatures also hierarchically represented systems-level parameters associated with PBMC including dysregulated cytokines, genes, pathways, networks of pathways/concepts, immune status, and cell types. Proof-of-principle confirmatory observations included PBMC-associated increases in ACE2 HGNC, cytokine storm-associated IL6 HGNC, enhanced innate immunity (macrophages and neutrophils), and lower adaptive T and B cell immunity in patients with acute-like disease compared to those with recovery-like disease. Patients in the recovery-like stage had significantly enhanced TNF HGNC, IFN-g HGNC, anti-viral, HLA-DQA1 HGNC, and HLA-F HGNC gene expression and cytolytic activity, and reduced pro-viral gene expression compared to those in the acute-like stage in PBMC. Besides, PBMC-derived surrogate-based approach revealed overlapping genes associated with comorbidities (associated diabetes MESHD), and disease-like symptoms (associated with thromboembolism MESHD, pneumonia MESHD, lung disease MESHD and septicaemia MESHD). Overall, our study involving PBMC-based RNA profiling may further help understand complex and variable systems-wide responses displayed by coronavirus-infected MESHD patients.

    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.

The ZB MED preprint Viewer preVIEW includes all COVID-19 related preprints from medRxiv and bioRxiv, from ChemRxiv, from ResearchSquare, from arXiv and from Preprints.org and is updated on a daily basis (7am CET/CEST).
The web page can also be accessed via API.

Sources


Annotations

All
None
MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


Export subcorpus as...

This service is developed in the project nfdi4health task force covid-19 which is a part of nfdi4health.

nfdi4health is one of the funded consortia of the National Research Data Infrastructure programme of the DFG.