Corpus overview


Overview

MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (5)

NSP5 (2)

ProteinN (2)

ProteinS1 (2)

NSP3 (1)


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SARS-CoV-2 Proteins
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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.

    IL-15 HGNC and sMAdCAM: Novel roles in COVID-19 MESHD pathogenesis

    Authors: Amit Kumar Singh; Nandini Jayant Kasarpalkar; Shilpa Dinesh Kumar Bhowmick; Gaurav Paradkar; Mayur Talreja; Karan Shah; Abhishek Tiwari; Harsha Chandrashekhar Palav; Snehal Nagendra Kaginkar; Rajiv Kulkarni; Ashwini Patil; Varsha Kalsurkar; Sachee Agrawal; Jayanthi Shastri; Rajesh Dere; Ramesh Bharmal; Smita D Mahale; Vikrant M Bhor; Vainav Patel

    doi:10.1101/2021.03.25.21254215 Date: 2021-03-29 Source: medRxiv

    Immune cell dysregulation and lymphopenia MESHD characterize COVID-19 MESHD pathology in moderate to severe disease. While underlying inflammatory factors have been extensively studied, homeostatic and mucosal migratory signatures remain largely unexplored as causative factors. In this study we evaluated the association of circulating IL-6 HGNC, soluble mucosal addressin cell adhesion molecule (sMAdCAM) and IL-15 HGNC with cellular dysfunction characterizing mild and hypoxemic stages of COVID-19 MESHD. A cohort of SARS-CoV-2 infected MESHD individuals (n=125) at various stages of disease progression together with healthy controls (n=16) were recruited from COVID Care Centres (CCCs) across Mumbai, India. Multiparametric flow cytometry was used to perform in-depth immune subset characterization and to measure plasma IL-6 HGNC levels. sMAdCAM, IL-15 HGNC levels were quantified using ELISA. Distinct depletion profiles, with relative sparing of CD8 HGNC effector memory and CD4 HGNC+ regulatory T cells was observed in hypoxemic disease MESHD within the lymphocyte compartment. An apparent increase in the frequency of intermediate monocytes characterized both mild as well as hypoxemic disease MESHD. IL-6 HGNC levels inversely correlated with those of sMAdCAM and both markers showed converse associations with observed lympho-depletion suggesting opposing roles in pathogenesis. Interestingly, IL-15 HGNC, a key cytokine involved in lymphocyte activation and homeostasis, was detected in symptomatic individuals but not in healthy controls or asymptomatic cases. Further, negative association of plasma IL-15 HGNC with depleted T, B and NK subsets suggested a compensatory production of this cytokine in response to the profound lymphopenia MESHD. Finally, higher levels of plasma IL-15 HGNC and IL-6 HGNC, but not sMAdCAM, were associated with longer duration of hospitalization.

    Authors: Natalia G Sampaio; Lise Chauveau; Jonny Hertzog; Anne Bridgeman; Gerissa Fowler; Jurgen P Moonen; Maeva Dupont; Rebecca A Russel; Marko Noerenberg; Jan Rehwinkel

    doi:10.1101/2021.03.26.437180 Date: 2021-03-27 Source: bioRxiv

    Human cells respond to infection by SARS-CoV-2, the virus that causes COVID-19 MESHD, by producing cytokines including type I and III interferons (IFNs) and proinflammatory factors such as IL6 HGNC and TNF HGNC. IFNs can limit SARS-CoV-2 replication but cytokine imbalance contributes to severe COVID-19 MESHD. We studied how cells detect SARS-CoV-2 infection MESHD. We report that the cytosolic RNA sensor MDA5 HGNC was required for type I and III IFN induction in the lung cancer MESHD cell line Calu-3 upon SARS-CoV-2 infection MESHD. Type I and III IFN HGNC induction further required MAVS HGNC and IRF3 HGNC. In contrast, induction of IL6 HGNC and TNF HGNC was independent of the MDA5 HGNC- MAVS HGNC- IRF3 HGNC axis in this setting. We further found that SARS-CoV-2 infection MESHD inhibited the ability of cells to respond to IFNs. In sum, we identified MDA5 HGNC as a cellular sensor for SARS-CoV-2 infection MESHD that induced type I MESHD and III IFNs.

    Mast Cells and COVID-19 MESHD: a case report implicating a role of mast cell activation in the prevention and treatment of Covid-19 MESHD

    Authors: Isabelle Brock; Anne Maitland

    doi:10.21203/rs.3.rs-330667/v2 Date: 2021-03-15 Source: ResearchSquare

    Coronavirus disease MESHD ( COVID-19 MESHD) is a heterogeneous syndrome MESHD following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD of the upper respiratory tract. ln adults, the clinical condition can range from asymptomatic cases to severe acute respiratory syndrome MESHD and multi-organ dysfunction MESHD. Those at risk of developing COVID-19 MESHD related hyperinflammatory syndrome MESHD likely had an ineffective, innate immune response to this novel pathogen. Mast cells are associated with the epithelium, contributing to tissue homeostasis and epithelial barrier defense. Equipped with an array of pathogen receptors, mast cells exhibit distinct cytokine profiles, dependent on the tissue and the triggered pathogen receptors. Following viral infections, mast cells produce pro-inflammatory chemical mediators, such as interleukin-1 (IL-1) and IL-6 HGNC, and these cytokines has been shown to be elevated in severe COVID-19 MESHD cases. Here, we present a case of a patient with a longstanding history of signs and symptoms, worrisome for a mast cell activation syndrome MESHD ( MCAS MESHD), but never had laboratory confirmation of this non-clonal mast cell activation disorder, until she contracted COVID-19 MESHD. This case illustrates the need to recognize the rate of mast cell activation in SARS-CoV-2 infection MESHD, not only to optimize anti-SARS-CoV-2 therapy, including the development of vaccine, but to potentially curb the risk of SARS­ CoV-2 triggered hyperinflammatory syndrome MESHD.

    Clinical course and risk factors for in-hospital mortality of 205 patients with SARS-CoV-2 pneumonia MESHD in Como, Lombardy Region, Italy

    Authors: Mauro Turrini; Angelo Gardellini; Livia Beretta; Lucia Buzzi; Stefano Ferrario; Sabrina Vasile; Raffaella Clerici; Andrea Colzani; Luigi Liparulo; Giovanni Scognamiglio; Gianni Imperiali; Giovanni Corrado; Antonella Strada; Marco Galletti; Nunzio Castiglione; Claudio Zanon

    doi:10.1101/2021.02.25.20134866 Date: 2021-03-05 Source: medRxiv

    Importance: With randomized clinical trials ongoing and vaccine still a long distance away, efforts to repurpose old medications used for other diseases provide hope for treatment of COVID-19 MESHD. Objectives: To examine the risk factors for in-hospital mortality and describe the effectiveness of different treatment strategies in a real-life setting of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia MESHD. Design: Real-life single-center study during the Lombardy COVID-19 MESHD outbreak. Setting: Valduce Hospital in Como, Lombardy Region, Italy. Participants: 205 laboratory-confirmed patients presenting with SARS-Cov-2 pneumonia MESHD requiring hospitalization. Interventions: All patients received best supportive care and, based on their clinical needs and comorbidities, specific interventions that included the main drugs being tested for repurposing to treat COVID-19 MESHD, such as hydroxychloroquine, anticoagulation, antiviral drugs, steroids or interleukin-6 HGNC pathway inhibitors. Main outcomes and measures: Clinical, laboratory and treatment characteristics were analyzed with univariate and multivariate logistic regression methods to explore their impact on in-hospital mortality and compared with current literature data. Results: Univariate analyses for clinical variables showed prognostic significance for age equal or greater than 70 years (estimated 28-days survival: 21.4 vs 67.4%; p<0.0001), presence of 2 or more relevant comorbidities (35.3 vs 61.8%; p=0.0008), ratio of arterial oxygen partial pressure to fractional inspired oxygen (P/F) less than 200 at presentation (21-days survival: 14.7 vs 52.4%;p<0.0001), high levels of lactate dehydrogenase (LDH) (26.4 vs 65.3%; p=0.0001), and elevated C-reactive protein HGNC (CRP) values (25.4 vs 74.9%; p=0.0001), while no statistical significance was found for all the other clinical variables tested. At univariate analysis for the different treatment scheduled, prognostic significance for survival was showed for intermediate or therapeutic-dose anticoagulation (estimated 28-days survival: 37.1 vs 23.4%; p=0.0001), hydroxychloroquine (35.7 vs 27.3%; p=0.0029), early antiviral therapy with lopinavir/ritonavir (60.1 vs 22.4%; p<0.0001), late short-course of steroids (47.9 vs 18.2%; p<0.0001) or tocilizumab therapy (69.4 vs 29.4%; p=0.0059). Multivariable regression confirmed increasing odds of in-hospital death associated with age older than 70 years (odds ratio 3.26, 95% CI 1.81 - 5.86; p<0.0001) and showed a reduction in mortality for patients treated with anticoagulant (-0.37, 0.49 - 0.95; p=0.0273), antiviral (-1.22, 0.16 - 0.54; p<0.0001), or steroids (-0.59, 0.35 - 0.87; p=0.0117) therapy.

    Effect of SARS-CoV-2 proteins on vascular permeability

    Authors: Rossana Rauti; Meishar Shahoha; Yael Leichtmann-Bardoogo; Rami Nasser; Rina Tamir; Victoria Miller; Tal Babich; Kfir Shaked; Avner Ehrlich; Konstantinos Ioannidis; Yaakov Nahmias; Roded Sharan; Uri Ashery; Ben Meir Maoz

    doi:10.1101/2021.02.27.433186 Date: 2021-03-01 Source: bioRxiv

    SARS CoV 2 infection MESHD leads to severe disease associated with cytokine storm, vascular dysfunction MESHD, coagulation, and progressive lung damage MESHD. It affects several vital organs, seemingly through a pathological effect on endothelial cells. The SARS-CoV-2 genome encodes 29 proteins, whose contribution to the disease manifestations, and especially endothelial complications, is unknown. We cloned and expressed 26 of these proteins in human cells and characterized the endothelial response to overexpression of each, individually. Whereas most proteins induced significant changes in endothelial permeability, nsp2 HGNC, nsp HGNC5_c145a (catalytic dead mutant of nsp5 HGNC) and nsp7 also reduced CD31 HGNC, and increased von Willebrand MESHD factor expression and IL-6 HGNC, suggesting endothelial dysfunction. Using propagation-based analysis of a protein protein interaction (PPI) network, we predicted the endothelial proteins affected by the viral proteins that potentially mediate these effects. We further applied our PPI model to identify the role of each SARS CoV 2 protein in other tissues affected by COVID 19. Overall, this work identifies the SARS CoV 2 proteins that might be most detrimental in terms of endothelial dysfunction, thereby shedding light on vascular aspects of COVID 19.

    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.

    Exosomes from COVID-19 MESHD patients carry tenascin-C HGNC and fibrinogen-β in triggering inflammatory signals in distant organ cells

    Authors: Subhayan Sur; Mousumi B. Khatun; Robert Steele; Scott Isbell; Ranjit Ray; Ratna B Ray

    doi:10.1101/2021.02.08.430369 Date: 2021-02-09 Source: bioRxiv

    SARS-CoV-2 infection MESHD causes cytokine storm and overshoot immunity in humans; however, it remains to be determined whether genetic material of SARS-CoV-2 and/or virus induced soluble mediators from lung epithelial cells as natural host are carried out by macrophages or other vehicles at distant organs causing tissue damage. We speculated that exosomes as extracellular vesicles are secreted from SARS-CoV-2 infected MESHD cells may transport messages to other cells of distant organs leading to pathogenic consequences. For this, we took an unbiased proteomic approach for analyses of exosomes isolated from plasma of healthy volunteers and SARS-CoV-2 infected MESHD patients. Our results revealed that tenascin-C HGNC ( TNC HGNC) and fibrinogen-{beta} ( FGB HGNC) are highly abundant in exosomes from SARS-CoV-2 infected MESHD patient's plasma as compared to that of healthy normal controls. Since TNC HGNC and FGB HGNC stimulate pro-inflammatory cytokines via NF-kB pathway, we examined the status of TNF-a HGNC, IL-6 HGNC and CCL5 HGNC expression upon exposure of hepatocytes to exosomes from COVID-19 MESHD patients and observed significant increase when compared with that from healthy subjects. Together, our results demonstrated that soluble mediators, like TNC HGNC and FGB HGNC, are transported through plasma exosomes in SARS-CoV-2 infected MESHD patients and trigger pro-inflammatory cytokine expression in cells of distant organs in COVID-19 MESHD patients.

    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.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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