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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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    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.

    Disruption of the CCL5 HGNC/ RANTES HGNC- CCR5 HGNC Pathway Restores Immune Homeostasis and Reduces Plasma Viral Load in Critical COVID-19 MESHD

    Authors: Bruce Pattterson; Harish Seetthamraju; Kush Dhody; Michael Corley; Kazem Kazempour; Jay Lalezari; Alina Pang; Christopher Sugai; Edgar Francisco; Amruta Pise; Hallison Rodrigues; Matthew Ryou; Helen Wu; Gabriela Webb; Byung Park; Scott Kelly; Nader Pourhassan; Alena Lelic; Lama Kdouh; Monica Herrera; Eric Hall; Enver Aklin; Lishomwa Ndhlovu; Jonah Sacha

    doi:10.21203/rs.3.rs-26517/v1 Date: 2020-05-02 Source: ResearchSquare

    Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), the causative agent of coronavirus disease 2019 MESHD ( COVID-19 MESHD), is now pandemic with nearly three million cases reported to date1. Although the majority of COVID-19 MESHD patients experience only mild or moderate symptoms, a subset will progress to severe disease with pneumonia MESHD and acute respiratory distress syndrome MESHD ( ARDS MESHD) requiring mechanical ventilation2. Emerging results indicate a dysregulated MESHD immune response characterized by runaway inflammation MESHD, including cytokine release syndrome (CRS), as the major driver of pathology in severe COVID-19 MESHD3,4. With no treatments currently approved for COVID-19 MESHD, therapeutics to prevent or treat the excessive inflammation MESHD in severe disease caused by SARS-CoV-2 infection MESHD are urgently needed. Here, in 10 terminally-ill, critical COVID-19 MESHD patients we report profound elevation of plasma IL-6 HGNC and CCL5 HGNC ( RANTES HGNC), decreased CD8 HGNC+ T cell levels, and SARS-CoV-2 plasma viremia MESHD. Following compassionate care treatment with the CCR5 HGNC blocking antibody leronlimab, we observed complete CCR5 HGNC receptor occupancy on macrophage and T cells, rapid reduction of plasma IL-6 HGNC, restoration of the CD4 HGNC/ CD8 HGNC ratio, and a significant decrease in SARS-CoV-2 plasma viremia MESHD. Consistent with reduction of plasma IL-6 HGNC, single-cell RNA-sequencing revealed declines MESHD in transcriptomic myeloid cell clusters expressing IL-6 HGNC and interferon-related genes. These results demonstrate a novel approach to resolving unchecked inflammation MESHD, restoring immunologic deficiencies MESHD, and reducing SARS-CoV-2 plasma viral load via disruption of the CCL5 HGNC- CCR5 HGNC axis, and support randomized clinical trials to assess clinical efficacy of leronlimab-mediated inhibition of CCR5 HGNC for COVID-19 MESHD.

    Could Unconventional Immunomodulatory Agents Help Alleviate COVID-19 MESHD Symptoms and Severity?

    Authors: Stephen Mamber; Steven Krakowka; Jeffrey Osborn; Lloyd Saberski; Ryan Rhodes; Albert Dahlberg; Kara Fitzgerald; Neal Wright; Sarah Beseme; John McMichael

    id:202004.0014/v2 Date: 2020-04-27 Source: Preprints.org

    Severe acute respiratory syndrome coronavirus 2 MESHD (SARS coronavirus 2 or SARS-CoV-2) is the cause of the respiratory infection MESHD known as COVID-19 MESHD. From an immunopathological standpoint, coronaviruses such as SARS-CoV-2 induce an increase in a variety of T-helper 1 ( Th1 HGNC) and inflammatory cytokines and chemokines including interleukins IL-1 HGNC, IL-6 HGNC, CCL2 HGNC protein and CXCL10 HGNC protein. In the absence of proven antiviral agents or an effective vaccine, substances with immunomodulatory activity may be able to inhibit inflammatory and Th1 HGNC cytokines and/or yield an anti-inflammatory and/or Th2 immune response to counteract COVID-19 MESHD symptoms and severity. This report briefly describes four unconventional but commercially accessible immunomodulatory agents that could be employed in clinical trials to evaluate their effectiveness at alleviating disease symptoms and severity: Low-dose oral interferon-alpha, microdose DNA, low-dose thimerosal and phytocannabinoids.

    Involvement of Bradykinin HGNC and Folate receptor in calming the SARS-COV2 cytokine storm: Lessons learnt from lung cancer

    Authors: Pruthvi Gowda; Ellora Sen

    doi:10.21203/rs.3.rs-23656/v1 Date: 2020-04-17 Source: ResearchSquare

    Background: Severe acute respiratory syndrome MESHD coronavirus (SARS-CoV2) is a highly pathogenic respiratory virus that causes morbidity and mortality in humans. The lungs are the major pathological target of SARS-CoV infection MESHD. The pathological derangements, aberrant signalling and dysregulated inflammation MESHD characteristics of lung cancer MESHD have marked similarities with the clinical manifestation of SARS-COV2 infection MESHD. As heightened inflammatory response is a key feature of both SARS-CoV infection and lung cancer MESHD and given the intriguing commonalities between the two, we analysed the RNA sequence dataset from lung cancer MESHD patients to get a better understanding of the critical regulators of inflammation MESHD in SAR-COV2. Methods: The Cancer Genome Atlas (TCGA) data sets of lung cancer MESHD were analyzed for correlations between ACE2 HGNC, Bradykinin HGNC, and other genes associated with inflammatory responses.Results: TCGA dataset analysis indicated an inverse correlation between ACE2 HGNC and Bradykinin Receptor 1 HGNC ( BDKRB1 HGNC), IL-6 HGNC and IFNg HGNC in lung adenocarcinoma. A positive correlation between EGF, FOLR1 HGNC, MAOA HGNC, NOSTRIN HGNC, MARC2 HGNC, PHKD1, and ACE2 HGNC was noted Summary: Our analysis has identified a common (i) ACE2 HGNC- BDKRB1 HGNC-inflammatory network and (ii) FOLR1 HGNC-Nitric oxide cross-talk in lung cancer MESHD and SARS-CoV2. Better understanding of the convergences between critical players in these networks would enable efficient repurposing of approved lung cancer MESHD therapeutics for COVID-19 MESHD infection. 

    Clinical characteristics of 34 COVID-19 MESHD patients admitted to ICU in Hangzhou, China

    Authors: Yi Zheng; Lijun Sun; Mi Xu; Jian Pan; Yuntao Zhang; Xueling Fang; Qiang Fang; Hongliu Cai

    doi:10.1101/2020.04.12.20062604 Date: 2020-04-15 Source: medRxiv

    Introduction: The purpose of the study was to summarize the clinical and laboratory characteristics of the coronavirus disease 2019 MESHD patients admitted to intensive care unit. Methods: We tracked the data until March 5, 2020. The cases in our cohort were divided into cases only received noninvasive ventilation (NIV) and cases required invasive mechanical ventilation (IMV). The characteristics between the two groups were compared. Results: 34 cases were included in the study. The complications rate (including, acute liver injury MESHD, acute cardiac injury MESHD and acute kidney injury MESHD) were higher in IMV cases. Lymphocytopenia and neutrophilia occurred in most cases in both groups on the admission day, however, lymphocyte levels dropped progressively and more severe lymphopenia MESHD occurred in IMV group. Increased amounts of plasma IL-6 HGNC and IL-10 HGNC were found in both groups on the admission day, the progressive decrease of which occurred in NIV cases rather than IMV cases, and the levels were higher in IMV cases during hospitalization. Conclusions: Lymphocytopenia MESHD, neutrophilia, and increase of IL-6 HGNC and IL-10 HGNC occurred in SARS-CoV-2 infected MESHD patients in ICU, however, the dynamics of those were significantly different in IMV cases and NIV cases during hospitalization.

    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.

    Virus-host interactome and proteomic survey of PMBCs from COVID-19 MESHD patients reveal potential virulence factors influencing SARS-CoV-2 pathogenesis

    Authors: Qiming Liang; Jingjiao Li; Mingquan Guo; Xiaoxu Tian; Chengrong Liu; Xin Wang; Xing Yang; Ping Wu; Zixuan Xiao; Yafei Qu; Yue Yin; Joyce Fu; Zhaoqin Zhu; Zhenshan Liu; Chao Peng; Tongyu Zhu

    doi:10.1101/2020.03.31.019216 Date: 2020-04-02 Source: bioRxiv

    The ongoing coronavirus disease MESHD ( COVID-19 MESHD) pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 MESHD (SARS-CoV-2) is a global public health concern due to relatively easy person-to-person transmission and the current lack of effective antiviral therapy. However, the exact molecular mechanisms of SARS-CoV-2 pathogenesis remain largely unknown. We exploited an integrated proteomics approach to systematically investigate intra-viral and virus-host interactomes for the identification of unrealized SARS-CoV-2 host targets and participation of cellular proteins in the response to viral infection using peripheral blood mononuclear cells (PBMCs) isolated from COVID-19 MESHD patients. Using this approach, we elucidated 251 host proteins targeted by SARS-CoV-2 and more than 200 host proteins that are significantly perturbed in COVID-19 MESHD derived PBMCs. From the interactome, we further identified that non-structural protein nsp9 and nsp10 interact with NKRF HGNC, a NF-[Kcy]B repressor, and may precipitate the strong IL-8 HGNC/ IL-6 HGNC mediated chemotaxis of neutrophils and overexuberant host inflammatory response observed in COVID-19 MESHD patients. Our integrative study not only presents a systematic examination of SARS-CoV-2-induced perturbation of host targets and cellular networks to reflect disease etiology, but also reveals insights into the mechanisms by which SARS-CoV-2 triggers cytokine storms and represents a powerful resource in the quest for therapeutic intervention.

    COVID-19 MESHD Treatment: Close to a Cure? – A Rapid Review of Pharmacotherapies for the Novel Coronavirus

    Authors: Yang Song; Min Zhang; Ling Yin; Kunkun Wang; Yiyi Zhou; Mi Zhou; Yun Lu

    id:10.20944/preprints202003.0378.v1 Date: 2020-03-26 Source: Preprints.org

    Currently, there is no specific treatment for COVID-19 MESHD proven by clinical trials. WHO and CDC guidelines therefore endorse supportive care only. However, frontline clinicians have been applying several virus-based and host-based therapeutics in order to combat SARS-CoV-2. Medications from COVID-19 MESHD case reports, observational studies and the COVID-19 MESHD Treatment Guideline issued by the China's National Health Commission (7th edition published March 3rd, 2020. Edited translation attached) are evaluated in this review. Key evidence from relevant in vitro researches, animal models and clinical studies in SARS-CoV-2, SARS-CoV and MERS-CoV MESHD are examined. Antiviral therapies remdesivir, lopinavir/ritonavir and umifenovir, if considered, could be initiated before the peak of viral replication for optimal outcomes. Ribavirin may be beneficial as an add-on therapy and is ineffective as a monotherapy. Corticosteroids use should be limited without indicating comorbidities. IVIG is not recommended due to lack of data in COVID-19 MESHD. Xuebijing may benefit patients with complications of bacterial pneumonia MESHD or sepsis MESHD. The efficacy of interferon is unclear due to conflicting outcomes in SARS and MERS studies. Chloroquine and hydroxychloroquine have shown in vitro inhibition of SARS-CoV-2 and may be beneficial as both prophylactic and treatment therapy. For patients who developed cytokine release syndrome, interleukin-6 HGNC inhibitors may be beneficial. Given the rapid disease spread and increasing mortality, active treatment with readily available medications may be considered timely prior to disease progression.

    Potential Factors for Prediction of Disease Severity of COVID-19 MESHD Patients

    Authors: huizheng zhang; xiaoying wang; zongqiang fu; ming luo; zhen zhang; ke zhang; ying he; dongyong wan; liwen zhang; jing wang; xiaofeng yan; mei han; yaokai chen

    doi:10.1101/2020.03.20.20039818 Date: 2020-03-23 Source: medRxiv

    Objective Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is an escalating global epidemic caused by SARS-CoV-2, with a high mortality in critical patients. Effective indicators for predicting disease severity in SARS-CoV-2 infected MESHD patients are urgently needed. MethodsIn this study, 43 COVID-19 MESHD patients admitted in Chongqing Public Health Medical Center were involved. Demographic data, clinical features, and laboratory examinations were obtained through electronic medical records. Peripheral blood specimens were collected from COVID-19 MESHD patients and examined for lymphocyte subsets and cytokine profiles by flow cytometry. Potential contributing factors for prediction of disease severity were further analyzed. ResultsA total of 43 COVID-19 MESHD patients were included in this study, including 29 mild patients and 14 sever patients. Severe patients were significantly older (61.9{+/-}9.4 vs 44.4{+/-}15.9) and had higher incidence in co-infection MESHD with bacteria compared to mild group (85.7%vs27.6%). Significantly more severe patients had the clinical symptoms of anhelation (78.6%) and asthma MESHD (71.4%). For laboratory examination, 57.1% severe cases showed significant reduction in lymphocyte count. The levels of Interluekin-6 ( IL6 HGNC), IL10 HGNC, erythrocyte sedimentation rate (ESR) and D-Dimer (D-D) were significantly higher in severe patients than mild patients, while the level of albumin ( ALB HGNC) was remarkably lower in severe patients. Further analysis demonstrated that ESR, D-D, age, ALB HGNC and IL6 HGNC were the major contributing factors for distinguishing severe patients from mild patients. Moreover, ESR was identified as the most powerful factor to predict disease progression of COVID-19 MESHD patients. ConclusionAge and the levels of ESR, D-D, ALB HGNC and IL6 HGNC are closely related to the disease severity of COVID-19 MESHD patients. ESR can be used as a valuable indicator for distinguishing severe COVID-19 MESHD patients in early stage, so as to increase the survival of severe patients.

    Clinical Characteristics of SARS-CoV-2 Pneumonia Compared to Controls in Chinese Han Population

    Authors: Yang Xu; Yi-rong Li; Qiang Zeng; Zhi-bing Lu; Yong-zhe Li; Wei Wu; Sheng-yong Dong; Gang Huang; Xing-huan Wang

    doi:10.1101/2020.03.08.20031658 Date: 2020-03-10 Source: medRxiv

    Background In December 2019, novel coronavirus (SARS-CoV-2) infected pneumonia MESHD occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of SARS-CoV-2 pneumonia MESHD without comorbidities compared to normal controls in Chinese Han population is limited. Our objective is to describe the epidemiological and clinical characteristics of SARS-CoV-2 pneumonia MESHD without comorbidities compared to normal controls in the Chinese Han population. Methods Retrospective, multi-center case series of the 69 consecutive hospitalized patients with confirmed SARS-CoV-2 pneumonia MESHD, from February 7 to February 28, 2020; final date of follow-up was February 29, 2020. Results The study population included 69 hospitalized patients with confirmed SARS-CoV-2 pneumonia MESHD without comorbidities and 14,117 normal controls. 50.7% patients were male and 49.3% were female; 1.5% patients were asymptomatic cases, 63.8% patients were mild cases, and 36.2% patients were severe or critical cases. Compared with mild patients (n = 44), severe or critical patients (n = 25) were significantly older (median age, 67 years [IQR, 58-79] vs. 49 years [IQR, 36-60]; P < 0.01). Fever MESHD was present in 98.6% of the patients. The second most common symptom was cough (62.3%), fatigue MESHD (58.0%), sputum (39.1%), and headache MESHD (33.3%). The median incubation period was 4 days (IQR, 2 to 7). Leukocyte count was 74.1% of normal controls and lymphocyte count was 45.9% of normal controls. The phenomenon of lymphocyte depletion ( PLD HGNC) observed in severe or critical cases in 100%. Levels of lactate dehydrogenase, D-dimer, procalcitonin, and interleukin-6 HGNC were showed significant differences between mild and severe or critical cases. Chest computed tomographic scans showed bilateral patchy patterns (49.3%), local patchy shadowing (29.0%), and ground glass opacity (21.7%). 7.3% patients were diagnosed ARDS, 7.3% patients were diagnosed acute cardiac injury MESHD (troponin I >28 pg/mL) and 4.4% patients were diagnosed fungal infections MESHD or shock MESHD. 4.3% patients have been discharged; 1.5% patient had died; 1.5% patient had recovery. Conclusions In this multicenter case series of 69 patients without comorbidities, the full spectrum of asymptomatic, mild, severe, and critical cases is described. 50.7% patients were male and 49.3% were female; 1.5% patients were asymptomatic cases, 63.8% patients were mild cases, and 36.2% patients were severe or critical cases. 4.3% patients have been discharged; 1.5% patient had died; 1.5% patient had recovery. Among the 25 patients with severe or critical disease MESHD, 12.0% patients were underwent non-invasive mechanical ventilation, 8.0% patients underwent invasive mechanical ventilation, and 4.0% patients died.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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