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HGNC Genes

SARS-CoV-2 proteins

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    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.

    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.

    Increased Interleukin-6 HGNC and Macrophage Chemoattractant Protein-1 are associated with Respiratory Failure in COVID-19 MESHD 

    Authors: Marthe Jørgensen; Jan Cato Holter; Erik Egeland Christensen; Camilla Schjalm; Kristian Tonby; Søren Erik Pischke; Synne Jenum; Linda G Skeie; Sarah Nur; Andreas Lind; Hanne Opsand; Tone Burvald Enersen; Ragnhild Grøndahl; Anne Hermann; Susanne Dudman; Fredrik Müller; Thor Ueland; Tom Eirik Mollnes; Pål Aukrust; Lars Heggelund; Aleksander Rygh Holten; Anne Ma Dyrhol-Riise

    doi:10.21203/rs.3.rs-39162/v1 Date: 2020-06-30 Source: ResearchSquare

    Background: In SARS-CoV-2 infection MESHD ARS-CoV-2 infection MESHDthere is an urgent need to identify patients that will progress to severe COVID-19 MESHD and may benefit from targeted treatment.Objectives: Analyze plasma cytokines in COVID-19 MESHD patients and investigate their association with r espiratory failure MESHD(R F) MESHD and treatment in Intensive Care Unit (ICU). Method: Hospitalized patients (n=34) with confirmed COVID-19 MESHD were recruited into a prospective cohort study. Clinical data and blood samples were collected at inclusion and after 2-5 and 7-10 days. R F MESHDwas defined as PaO2/FiO2 ratio (P/F) <40kPa. Plasma cytokines were analyzed by a Human Cytokine 27-plex assay. Measurements and Results:  COVID-19 MESHD patients with R F MESHDand/or treated in ICU showed overall increased systemic cytokine levels. Plasma I L-6, HGNC I L-8, HGNC G -CSF, HGNC M CP-1, HGNC M IP-1α HGNClevels were negatively correlated with P/F, whereas combinations of I L-6, HGNC I P-10, HGNC I L-1ra HGNCand M CP-1 HGNCshowed the best association with R F MESHDin ROC analysis (AUC 0.79-0.80, p<0.05). During hospitalization the decline was most significant for I P-10 HGNC(P<0.001). Conclusion: Elevated levels of pro-inflammatory cytokines were present in patients with severe COVID-19 MESHD. I L-6 HGNCand M CP-1 HGNCwere inversely correlated with P/F with the largest AUC in ROC analyses and should be further explored as biomarkers to identify patients at risk for severe R F MESHDand as targets for improved treatment strategies. 

    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
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SARS-CoV-2 Proteins


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