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SARS-CoV-2 proteins

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    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/rs.3.rs-117894/v1 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.

    Resistance of endothelial cells to SARS-CoV-2 infection MESHD in vitro

    Authors: Blerina Ahmetaj-Shala; Thomas P Peacock; Laury Baillon; Olivia Swann; Hime Gashaw; Wendy S Barclay; Jane A. Mitchell; Chiara Piubelli; Greta Bergamaschi; Marcella Chiari; Alessandro Gori; Marina Cretich

    doi:10.1101/2020.11.08.372581 Date: 2020-11-09 Source: bioRxiv

    Rationale: The secondary thrombotic MESHD/vascular clinical syndrome of COVID-19 MESHD suggests that SARS-CoV-2 infects MESHD not only respiratory epithelium but also the endothelium activating thrombotic MESHD pathways, disrupting barrier function and allowing access of the virus to other organs of the body. However, a direct test of susceptibility to SARS-CoV-2 of authentic endothelial cell lines has not been performed. Objective: To determine infectibility of primary endothelial cell lines with live SARS-CoV-2 and pseudoviruses expressing SARS-CoV-2 spike PROTEIN protein. Methods and Results: Expression of ACE2 HGNC and BSG pathways genes was determined in three types of endothelial cells; blood outgrowth, lung microvascular and aortic endothelial cells. For comparison nasal epithelial cells, Vero E6 cells (primate kidney fibroblast cell line) and HEK 293T cells (human embryonic kidney cells) transfected with either ACE2 HGNC or BSG were used as controls. Endothelial and Vero E6 cells were treated with live SARS-CoV-2 virus for 1 hour and imaged at 24 and 72 hours post infection. Pseudoviruses containing SARS-CoV-2, Ebola and Vesicular Stomatis Virus MESHD glycoproteins were generated and added to endothelial cells and HEK 239Ts for 2 hours and infection measured using luminescence at 48 hours post infection. Compared to nasal epithelial cells, endothelial cells expressed low or undetectable levels of ACE2 HGNC and TMPRSS2 HGNC but comparable levels of BSG, PPIA HGNC and PPIB HGNC. Endothelial cells showed no susceptibility to live SARS-CoV-2 or SARS-CoV-2 pseudovirus (but showed susceptibility to Ebola and Vesicular Stomatitis Virus MESHD). Overexpression of ACE2 HGNC but not BSG in HEK 239T cells conferred SARS-CoV-2 pseudovirus entry. Endothelial cells primed with IL-1b HGNC remained resistant to SARS-CoV-2. Conclusion: Endothelial cells are resistant to infection with SARS-CoV-2 virus MESHD, in line with relatively low levels of ACE2 HGNC and TMPRSS2 HGNC, suggesting that the vascular dysfunction MESHD and thrombosis MESHD seen in severe COVID-19 MESHD is a result of factors released by adjacent infected cells (e.g. epithelial cells) and/or circulating, systemic inflammatory mediators.

    Host metabolite-cytokine correlation landscape in SARS-CoV-2 infection MESHD

    Authors: Nan Xiao; Meng Nie; Huanhuan Pang; Bohong Wang; Jieli Hu; Xiangjun Meng; Ke Li; Xiaorong Ran; Quanxin Long; Haijun Deng; Ni Tang; Ailong Huang; Zeping Hu

    doi:10.21203/rs.3.rs-91866/v1 Date: 2020-10-13 Source: ResearchSquare

    The systemic cytokine release syndrome (CRS) is a major cause of the multi-organ injury MESHD and fatal outcome induced by SARS-CoV-2 infection MESHD in severe COVID-19 MESHD patients. It has been well-known that metabolism plays a role in modulating the immune responses in infectious diseases MESHD. Yet, how the host metabolism correlates with CRS in COVID-19 MESHD patients and how the perturbed metabolites affect the cytokine release remains unclear. Here, we performed both metabolomics and cytokine/chemokine profiling on serum samples from the same cohort of healthy controls, mild and severe COVID-19 MESHD patients and delineated the global metabolic and immune response landscape along disease progression. Intriguingly, the correlation analysis revealed the tight link between metabolites and proinflammatory cytokines and chemokines, such as IL-6 HGNC, M-CSF HGNC, IL-1α HGNC, IL-1β HGNC, implying the potential regulatory role of arginine metabolism, tryptophan metabolism, and purine metabolism in hyperinflammation. Importantly, we demonstrated that targeting metabolism markedly modulated the proinflammatory cytokines release by PBMCs isolated from SARS-CoV-2-infected rhesus MESHD macaques ex vivo. Beyond providing a comprehensive resource of metabolism and immunology data of SARS-CoV-2 infection MESHD, our study showed that metabolic alterations can be potentially exploited to develop novel strategy for the treatment of fatal CRS in COVID-19 MESHD.

    Clinical characteristics, outcomes and follow-up of COVID-19 MESHD infection in cancer patients

    Authors: Minghao Fang; Jianmin Ling; Yanqing Wu; Zhaohua Wang; Le Yang

    doi:10.21203/rs.3.rs-33276/v1 Date: 2020-06-04 Source: ResearchSquare

    Purpose: The study is to describe the clinical characteristics, outcomes and follow-up  of cancer MESHD patients with COVID-19 MESHD. Methods: Clinical records, demographic data, signs and symptoms, laboratory results, cytokine profiles, chest CT scans, comorbidities, treatments, clinical outcomes, and RT-PCR of SARS-CoV-2 after discharge were retrospectively collected for fifty-six cancer MESHD patients with laboratory-confirmed COVID-19 MESHD pneumonia MESHD who were admitted to Tongji Hospital of Huazhong University of Science and Technology, Wuhan, China, from Feb 1 to Apr 1 HGNC, 2020. Evidence of cytokine profiles were assessed by testing for the IL1β HGNC, IL2R HGNC, IL6 HGNC, IL8 HGNC, IL10 HGNC, and TNF - α HGNC in the peripheral blood of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infected cancer MESHD patients. Results: Of 2143 patients with COVID-19 MESHD, 56 cancer MESHD patients were included. The patients were divided into two groups, as cancer MESHD survivors, and cancer MESHD non-survivors. 12 (21%) patients with lymphopenia MESHD (0.5 [0.3-0.7]) had died during hospital stay. In non-survivors, IL2R HGNC, IL6 HGNC, and IL10 HGNC were higher. 3(6.8%) cancer MESHD survivors with COVID-19 MESHD had positive RT-PCR test results again shortly after discharge. Conclusion: The mortality rate of COVID-19 MESHD among cancer MESHD patients are considerable. Cancer non-survivors are characterized by more severe lymphopenia MESHD and a higher levels of cytokines. Recovered cancer MESHD survivors still may be virus carriers.

    Lysosomotropic Active Compounds—Hidden Protection against COVID-19 MESHD / SARS-CoV-2 Infection MESHD?

    Authors: Markus Blaess; Lars Kaiser; Martin Sauer; Hans-Peter Deigner

    id:10.20944/preprints202005.0061.v1 Date: 2020-05-05 Source: Preprints.org

    The COVID-19 MESHD COVID-19 MESHD pandemic is one of the largest challenges in medicine and health care worldwide in recent decades, and it is infecting and killing increasing numbers of people every day. In this paper, we discuss the possible relationships among lysosomotropism, increasing lysosomal pH, and the SARS-CoV-2 infection MESHD and disease process, and we deduce a possible approach for treatment and prophylaxis. Lysosomotropism is a biological characteristic of small molecules, such as (hydroxyl)chloroquine, amitriptyline, NB 06, or sertraline, which is present in addition to intrinsic receptor-mediated or enzymatic pharmacological effects. Lysosomotropic compounds affect prominent inflammatory messengers, such as IL1B HGNC, CCL4 HGNC, CCL20 HGNC, and IL6 HGNC, as well as cathepsin L HGNC dependent viral entry (fusion) into host cells. Therefore, this heterogeneous group of compounds is a promising candidate for the prevention and treatment of SARS-CoV-2 infections MESHD, as well as influenza A infections and cytokine release syndrome (CRS) triggered by bacterial or viral infections MESHD. Patients who have already taken medications with lysosomotropic compounds for other pre-existing conditions may benefit from this treatment in the COVID-19 pandemic MESHD. Increased lysosomal pH levels play an important role in the disease process in common skin disorders MESHD, such as psoriasis MESHD and atopic dermatitis MESHD, thus suggesting that affected individuals might benefit from their particular conditions in the COVID-19 pandemic MESHD. We suggest data analysis of patients with these diseases, and who are treated with lysosomotropic compounds, and, if the results are promising, subsequent clinical testing of off-label therapy with clinically approved lysosomotropic compounds in the current COVID-19 pandemic MESHD and future influenza A pandemics.

    Bulk and single-cell gene expression profiling of SARS-CoV-2 infected human cell lines identifies molecular targets for therapeutic intervention

    Authors: Emanuel Wyler; Kirstin Mösbauer; Vedran Franke; Asija Diag; Lina Theresa Gottula; Roberto Arsie; Filippos Klironomos; David Koppstein; Salah Ayoub; Christopher Buccitelli; Anja Richter; Ivano Legnini; Andranik Ivanov; Tommaso Mari; Simone Del Giudice; Jan Patrick Papies; Marcel Alexander Müller; Daniela Niemeyer; Matthias Selbach; Altuna Akalin; Nikolaus Rajewsky; Christian Drosten; Markus Landthaler

    doi:10.1101/2020.05.05.079194 Date: 2020-05-05 Source: bioRxiv

    The coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing global health threat with more than two million infected people since its emergence in late 2019. Detailed knowledge of the molecular biology of the infection is indispensable for understanding of the viral replication, host responses, and disease progression. We provide gene expression profiles of SARS-CoV and SARS-CoV-2 infections MESHD SARS-CoV-2 infection MESHDs in three human cell lines (H1299, Caco-2 and Calu-3 cells), using bulk and single-cell transcriptomics. Small RNA profiling showed strong expression of the immunity and inflammation MESHD-associated microRNA miRNA-155 HGNC upon infection with both viruses. SARS-CoV-2 elicited approximately two-fold higher stimulation of the interferon response compared to SARS-CoV in the permissive human epithelial cell line Calu-3, and induction of cytokines such as CXCL10 HGNC or IL6 HGNC. Single cell RNA sequencing data showed that canonical interferon stimulated genes such as IFIT2 HGNC or OAS2 HGNC were broadly induced, whereas interferon beta HGNC ( IFNB1 HGNC) and lambda (IFNL1-4) were expressed only in a subset of infected cells. In addition, temporal resolution of transcriptional responses suggested interferon regulatory factors (IRFs) activities precede that of nuclear factor-{kappa}B ( NF-{kappa}B HGNC). Lastly, we identified heat shock protein 90 ( HSP90 HGNC) as a protein relevant for the infection. Inhibition of the HSP90 HGNC charperone activity by Tanespimycin/17-N-allylamino-17-demethoxygeldanamycin (17-AAG) resulted in a reduction of viral replication, and of TNF HGNC and IL1B HGNC mRNA levels. In summary, our study established in vitro cell culture models to study SARS-CoV-2 infection MESHD and identified HSP90 HGNC protein as potential drug target for therapeutic intervention of SARS-CoV-2 infection MESHD.

    An Update on SARS-COV-2/ COVID-19 MESHD with Particular Reference on Its Clinical Pathology, Pathogenesis, Immunopathology and Mitigation Strategies – A Review

    Authors: Kuldeep Dhama; Shailesh Kumar Patel; Mamta Pathak; Mohd. Iqbal Yatoo; Ruchi Tiwari; Yashpal Singh Malik; Rajendra Singh; Ranjit Sah; Ali A. Rabaan; D. Katterine Bonilla-Aldana; Alfonso J. Rodriguez-Morales

    id:10.20944/preprints202003.0348.v1 Date: 2020-03-23 Source: Preprints.org

    Coronavirus Disease 2019 MESHD ( COVID-19 MESHD), caused by a novel coronavirus named Severe Acute Respiratory Syndrome MESHD - Coronavirus-2 (SARS-CoV-2), emerged in early December 2019 in China and attained a pandemic situation worldwide by its rapid spread to nearly 167 countries with 287.239 confirmed cases and 11.921 human deaths with a case fatality rate (CFR) of around 4 per cent. Bats were considered as the reservoir host, and the search of a probable intermediate host is still going on. Animals have anticipated culprit of SARS-CoV-2 as of now. The disease is mainly manifested by pneumonia MESHD and related respiratory signs and symptoms, but the involvement of the gastrointestinal system and nervous system is also suggested. The severe form of the disease associated with death MESHD is mainly reported in older and immune-compromised patients with pre-existing disease history. Death MESHD in severe cases is attributed to respiratory failure MESHD associated with hyperinflammation. Cytokine storm syndrome associated with rampant inflammation MESHD in response to SARS-CoV-2 infection MESHD is considered as the leading killer of COVID-19 MESHD patients. COVID-19 MESHD patients were reported with higher levels of many pro-inflammatory cytokines and chemokines like IFN-g HGNC, IL-1b HGNC, IP-10 HGNC, and MCP-1 HGNC. Furthermore, severe cases of COVID-19 MESHD revealed higher levels of TNF-α HGNC, G-CSF HGNC, and MIP-1A HGNC. Blood profile of the COVID-19 MESHD patients exhibits lymphopenia MESHD, leucopenia, thrombocytopenia MESHD and RNAaemia along with increased levels of aspartate aminotransferase. SARS-CoV-2 infection MESHD in pregnant women does not lead to fetus mortalities unlike other zoonotic coronaviruses like SARS-CoV and MERS-CoV, with no evidence of intrauterine transmission to neonates. Rapid and confirmatory diagnostics have been developed, and high efforts are being made to develop effective vaccines and therapeutics. In the absence of any virus-specific therapeutic, internationally health care authorities are recommending adoption of effective prevention and control measures to counter and contain this pandemic virus. This paper is an overview of this virus and the disease with a particular focus on SARS-COV-2 / COVID-19 MESHD clinical pathology, pathogenesis and immunopathology along with a few recent research developments.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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