Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinN (1)


SARS-CoV-2 Proteins
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    Regulation of Lysosome-Associated Membrane Protein 3 ( LAMP3 HGNC) in Lung Epithelial Cells by Coronaviruses (SARS-CoV-1/2) and Type I Interferon Signaling MESHD

    Authors: Ramana Chilakamarti

    doi:10.1101/2021.04.28.441840 Date: 2021-04-28 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a major risk factor for mortality and morbidity in critical care hospitals around the world. Lung epithelial type II cells play a major role in several physiological processes, including recognition and clearance of respiratory viruses as well as repair of lung injury MESHD in response to environmental toxicants. Gene expression profiling of lung epithelial type II-specific genes led to the identification of lysosomal-associated membrane protein 3 HGNC ( LAMP3 HGNC). Intracellular locations of LAMP3 HGNC include plasma membrane, endosomes, and lysosomes. These intracellular organelles are involved in vesicular transport and facilitate viral entry and release of the viral RNA into the host cell cytoplasm. In this study, regulation of LAMP3 HGNC expression in human lung epithelial cells by several respiratory viruses and type I interferon signaling was investigated. Coronaviruses including SARS-CoV-1 and SARS-CoV-2 MESHD significantly induced LAMP3 HGNC expression in lung epithelial cells within 24 hours after infection that required the presence of ACE2 HGNC viral entry receptor. Time-course experiments revealed that the induced expression of LAMP3 HGNC by SARS-CoV-2 was correlated with the induced expression of interferon-beta1 HGNC ( IFNB1 HGNC) and signal transducers and activator of transcription 1 ( STAT1 HGNC) mRNA levels. LAMP3 HGNC was also induced by direct IFN-beta treatment or by infection with influenza virus lacking the non-structural protein1(NS1) in NHBE bronchial epithelial cells. LAMP3 HGNC expression was induced in human lung epithelial cells by several respiratory viruses, including respiratory syncytial virus MESHD ( RSV MESHD) and the human parainfluenza virus 3 (HPIV3). Location in lysosomes and endosomes as well as induction by respiratory viruses and type I Interferon suggests that LAMP3 HGNC may have an important role in inter-organellar regulation of innate immunity and a potential target for therapeutic modulation in health and disease. Furthermore, bioinformatics revealed that a subset of lung type II cell genes were differentially regulated in the lungs of COVID-19 MESHD patients.

    Virtual Screening of Potential AEC2 Inhibitors for COVID-19 MESHD from Traditional Chinese Medicine

    Authors: Xiang He; JUNYI WANG; Lei Zhang; Qin Ran; Anying Xiong; Shengbin Liu; Dehong Wu; Bin Niu; Ying Xiong; Guoping Li

    doi:10.21203/ Date: 2021-01-11 Source: ResearchSquare

    Background: Angiotensin-converting enzyme 2 ( ACE2 HGNC), a negative regulator of the renin-angiotensin system and the severe acute respiratory syndrome-coronavirus MESHD ( SARS-CoV MESHD) and SARS-CoV-2 receptor, plays an important role in viral genome replication and immune response. ACE2 HGNC has been proposed as a potential therapeutic target. Traditional Chinese medicine (TCM) could be considered as a promising complementary therapeutic option in the management of COVID-19 MESHD. However, the active components and action mechanisms that account for its therapeutic effects remain controversial. Methods: ACE2 HGNC was employed as a target related to COVID-19 MESHD to explore the active ingredients from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. And the PharmMapper database and TCMSP database were used to predict the targets of the compounds. Moreover, the potential therapeutic targets of COVID-19 MESHD were acquired by intersection among genes differentially expressed in COVID-19 MESHD patients, genes screened from five public databases and genes targeted by active compounds. Finally, molecular docking verification and function analysis were performed.Results: In this study, puerarin, the common active compound for targeting ACE2 HGNC across the five TCMs (Radix Cyathulae, Flos Puerariac, Radix Bupleuri, Radix Puerariac and Radix Hemerocallis), was found. Due to the comprehensive analysis, we revealed that puerarin might prevent the entrance of SARS-CoV-2 entry into cells by blocking ACE2 HGNC, chiefly modulated the T cell immunity and regulate pro-inflammatory cytokine response by affecting TNF, STAT1 HGNC and RNASE3 HGNC. Conclusion: Taken together, the present study found that puerarin might have a therapeutic effect on COVID-19 MESHD through regulation of the immune system, inhibition of inflammation MESHD and prevention of virus entry into cells.

    Network of “drug-target-SARS-CoV-2 Related Genes” Through Integrated Analysis of Pharmacology and Geo Database

    Authors: Jin ping Hou; Yong heng Wang; Yu meng Chen; Yi hao Chen; Xiao Zhu; Rui si Qin; Tingting Chen

    doi:10.21203/ Date: 2020-11-28 Source: ResearchSquare

    BackgroundCoronavirus Disease MESHD Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) respiratory disease MESHD rapidly caused a global pandemic and social and economic disruption. The combination of Traditional Chinese medicine (TCM) and Conventional Western medicine (CWM) is more effective for COVID-19 MESHD treatment. Moreover, TCM and CWM are important data source for developing new drug targets and promote strategies treat SARS-CoV-2 infection MESHD SARS-CoV-2 infection MESHDs. However, many studies have analyzed the therapeutic mechanism of CWM or TCM alone for COVID-19 MESHD, it is still unclear the interaction mechanism between TCM and CWM on COVID-19 MESHD.MethodsThis paper integrates network pharmacology and GEO database to mine and identify COVID-19 MESHD molecular therapeutic targets, providing potential targets and new ideas for COVID-19 MESHD gene therapy and new drug development. It includes: 1) using TCMSP, TTD, PubChem and CTD databases to analyze drug interactions and associated phenotypes for SARS-CoV-2, to correlate drug and disease interaction mechanisms to screen key drug targets; 2) using GEO database to correlate differential genes and drug targets to screen potential antiviral gene therapy targets, to construct regulatory network and key points of SARS-CoV-2 therapeutic drugs; 3) using computer simulation of molecular docking to screen virus-related proteins for new drugs. ResultsIntegrated analysis of network pharmacology discovered that baicalein, estrone and quercetin are the pivotal active ingredients in TCM and CWM. Combining drug target genes in pharmacology database and virus induced genes in GEO database, the result showed the core hub genes related to COVID-19 MESHD: STAT1 HGNC, IL1B HGNC, IL6 HGNC, IL8 HGNC, PTGS2 HGNC and NFKBIA HGNC, and these genes were significantly downregulated in A549 and NHBE cells by SARS-CoV-2 infection MESHD. Moreover, chemical interaction and molecular docking analysis of hub genes showed that folic acid might as be potential therapeutic drug for COVID-19 MESHD treatment, and SARS-CoV-2 nucleocapsid phosphoprotein was a potential drug target. The network of “drug-target-SARS-CoV-2 related genes” provide noval potential compounds and targets for further studies of SARS-CoV-2.ConclusionsIntegrated analysis of network pharmacology and big data mining provided noval potential compounds and targets for further studies of SARS-CoV-2. Our research implied folic acid and SARS-CoV-2 N as therapeutic target in TCM and CWM. Our research also suggests that targeting SARS-CoV-2 N MESHD N protein PROTEIN is likely to be a common mechanism of TCM and CWM. On the one hand, the identification of pivotal genes provides a target for COVID-19 MESHD molecular therapy, on the other hand, it provides ideas for the analysis of interaction mechanism between virus and host.

    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:

    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/ 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. 

    Therapeutic Approaches for COVID-19 MESHD Based on the Dynamics of Interferon-mediated Immune Responses

    Authors: Farbod Shahabi nezhad; Pouria Mosaddeghi; Manica Negahdaripour; Zahra Dehghani; Mitra Farahmandnejad; Mohsen Moghadami; Navid Nezafat; Seyed Masoom Masoompour

    id:10.20944/preprints202003.0206.v2 Date: 2020-03-23 Source:

    As the outbreak of COVID-19 MESHD has accelerated, an urgent need for finding strategies to combat the virus is growing. Thus, gaining more knowledge on the pathogenicity mechanisms of SARS-CoV-2, the causing agent of COVID-19 MESHD, and its interaction with the immune system is of utmost importance. Although this novel virus is not well known yet, its structural and genetic similarity with SARS-CoV MESHD as well as the comparable pattern of age-mortality relations suggest that the previous findings on SARS can be applicable for COVID-19 MESHD. Therefore, a systems biology study was conducted to investigate the most important signaling pathways activated by the virus. The results were then validated through a literature review on COVID-19 MESHD and the other closely related viruses, SARS and MERS. Interferons have shown to play a crucial role in the defense against coronavirus diseases MESHD. CoV can impede the interferon induction in humans. Moreover, STAT1 HGNC, a key protein in the interferon-mediated immune response, is antagonized by the virus. This could explain the increased response threshold of immune cells to IFNs during CoV infections MESHD. A vivid correlation between the innate immune response threshold and the fatality rates in COVID-19 MESHD can be found. Differences in the dynamics of the interferon-related innate immune responses in children, adults, and elderly may explain the reported fatality rates. The increased mortality rates in the elderly can be explained by the higher threshold of interferon-mediated immune responses. Earlier induction of interferons in children and their less developed immune system could contribute to their near to zero fatality rate. Administration of interferon-inducing agents, such as poly (ICLC), could reduce the mortality of SARS at the very early stages of the disease. Interferon-γ combination with an interferon-I might induce synergistic effects and maximize the benefits. However, in-depth research is needed to validate it and determine the optimum dosage and timing to prevent unwanted results. Such interventions can act as a double-edged sword and aid the imbalance of the immune reactions, which may occur at the later stages of the disease. With the advancement of the disease and the virus overload, the responses would shift toward immnopathogenic over-reactions and probably cytokine storm. Moderating the activity of the immune system and supportive care in such conditions might be the optimum approach.

    Computational analysis of microRNA-mediated interactions in SARS-CoV-2 infection MESHD

    Authors: Muserref Duygu Sacar Demirci; Aysun Adan

    doi:10.1101/2020.03.15.992438 Date: 2020-03-17 Source: bioRxiv

    MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that have been found in more than 200 diverse organisms. Although it is still not fully established if RNA viruses could generate miRNAs that would target their own genes or alter the host gene expression, there are examples of miRNAs functioning as an antiviral defense mechanism. In the case of Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), there are several mechanisms that would make miRNAs impact the virus, like interfering with replication, translation and even modulating the host expression. In this study, we performed a machine learning based miRNA prediction analysis for the SARS-CoV-2 genome to identify miRNA-like hairpins and searched for potential miRNA - based interactions between the viral miRNAs and human genes and human miRNAs and viral genes. Our PANTHER gene function analysis results indicate that viral derived miRNA candidates could target various human genes involved in crucial cellular processes including transcription. For instance, a transcriptional regulator, STAT1 HGNC and transcription machinery might be targeted by virus-derived miRNAs. In addition, many known human miRNAs appear to be able to target viral genes. Considering the fact that miRNA-based therapies have been successful before, comprehending mode of actions of miRNAs and their possible roles during SARS-CoV-2 infections MESHD could create new opportunities for the development and improvement of new therapeutics.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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