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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (93)

NSP5 (14)

ProteinN (13)

ProteinE (13)

ComplexRdRp (10)


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SARS-CoV-2 Proteins
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    Nosocomial Pseudomonas aeruginosaregulates alginate biosynthesis and Type VI secretion system during adaptive and convergent evolution for coinfection in critically ill COVID-19 MESHD patients

    Authors: Zhao Cai; Xiangke Duan; Han Zhang; Shuhong Han; Kaiwei Yu; Yingdan Zhang; Yang Liu; Liang Yang

    doi:10.1101/2021.04.09.439260 Date: 2021-04-11 Source: bioRxiv

    COVID-19 pandemic MESHD has caused millions of death MESHD globally and caused huge impact on the health of infected MESHD patients. Shift in the lung microbial ecology upon such viral infection often worsens the disease MESHD and increases host susceptibility to secondary infections. Recent studies have indicated that bacterial coinfection is an unignorable factor contributing to the aggravation of COVID-19 MESHD and posing great challenge to clinical treatments. However, there is still a lack of in-depth investigation on the coinfecting bacteria in COVID-19 MESHD patients for better treatment of bacterial coinfection. With the knowledge that Pseudomonas aeruginosa is one of the top coinfecting pathogens, we analyzed the adaptation and convergent evolution of nosocomial Pseudomonas aeruginosa isolated from two critical COVID-19 MESHD patients in this study. We sequenced and compared the genomes and transcriptomes of Pseudomonas aeruginosa isolates longitudinally and parallelly for its evolutionary traits. Pseudomonas aeruginosa overexpressed alginate and attenuated Type VI secretion system MESHD (T6SS) during coinfection for excessive biofilm formation and suppressed virulence. Results of bacterial competition assay and macrophage cytotoxicity MESHD test indicated that Pseudomonas aeruginosa reduced its virulence towards both prokaryotic competitors and eukaryotic host through inhibiting its T6SS during evolution. Pseudomonas aeruginosa T6SS is thus one of the reasons for its advantage to cause coinfection in COVID-19 MESHD patients while the attenuation of T6SS could cause a shift in the microecological composition in the lung. Our study will contribute to the development of therapeutic measures and the discovery of novel drug target to eliminate Pseudomonas aeruginosa coinfection MESHD in COVID-19 MESHD patient.

    Human pulmonary artery endothelial cells upregulate ACE2 HGNC expression in response to iron-regulatory elements: potential implications for SARS-CoV-2 infection MESHD of vascular endothelial cells.

    Authors: Quezia K Toe; Theo Issitt; Abdul Mahomed; Ioannis Panselinas; Fatma Almaghlouth; Anne Burke-Gaffney; Stephen John Wort; Gregory J Quinlan

    doi:10.1101/2021.04.08.437687 Date: 2021-04-08 Source: bioRxiv

    Emerging studies from the ongoing covid-19 pandemic MESHD have implicated vascular dysfunction MESHD and endotheliitis MESHD in many patients presenting with severe disease. However, there is limited evidence for the expression of ACE2 HGNC (the principal co-receptor for Sars-Cov-2 cellular attachment) in vascular endothelial cells which has prompted the suggestion that the virus does not infect these cell types. However, the studies presented here demonstrate enhanced expression of ACE2 HGNC at the level of both mRNA and protein, in human pulmonary artery endothelial cells (PAECs) challenged with either IL-6 HGNC or hepcidin HGNC. Notably elevated levels both these iron-regulatory elements have been described in Covid-19 MESHD patients with severe disease and are further associated with morbidity and mortality. Additionally, levels of both IL-6 HGNC and hepcidin HGNC are often elevated in the elderly and in chronic disease MESHD settings, these populations being at greater risk of adverse outcomes from Sars-Cov-2 infection MESHD. A role for IL-6 HGNC and hepcidin HGNC as modulators of ACE2 HGNC expression seems plausible, additional, studies are required to determine if viral infection MESHD can be demonstrated in PAECs challenged with either of these iron-regulatory elements.

    Signatures of COVID-19 MESHD severity and immune response in the respiratory tract microbiome

    Authors: Carter Merenstein; Guanxiang Liang; Samantha A Whiteside; Ana G Cobián-Güemes; Madeline S Merlino; Louis J Taylor; Abigail Glascock; Kyle Bittinger; Ceylan Tanes; Layla A Khatib; Ayannah S Fitzgerald; Shantan Reddy; Amy E Baxter; Josephine R Giles; Derek A Oldridge; Nuala J Meyer; E. John Wherry; John E McGinniss; Frederic Bushman; Ronald G Collman

    doi:10.1101/2021.04.02.21254514 Date: 2021-04-05 Source: medRxiv

    Rationale: Viral infection of the respiratory tract can be associated with propagating effects on the airway microbiome, and microbiome dysbiosis MESHD may influence viral disease MESHD. Objective: To define the respiratory tract microbiome in COVID-19 MESHD and relationship disease severity, systemic immunologic features, and outcomes. Methods and Measurements: We examined 507 oropharyngeal, nasopharyngeal and endotracheal samples from 83 hospitalized COVID-19 MESHD patients, along with non-COVID patients and healthy controls. Bacterial communities were interrogated using 16S rRNA gene sequencing, commensal DNA viruses Anelloviridae and Redondoviridae were quantified by qPCR, and immune features were characterized by lymphocyte/neutrophil (L/N) ratios and deep immune profiling of peripheral blood mononuclear cells (PBMC). Main Results: COVID-19 MESHD patients had upper respiratory microbiome dysbiosis MESHD, and greater change over time than critically ill patients without COVID-19 MESHD. Diversity at the first time point correlated inversely with disease severity during hospitalization, and microbiome composition was associated with L/N ratios and PBMC profiles in blood. Intubated patients showed patient-specific and dynamic lung microbiome communities, with prominence of Staphylococcus. Anelloviridae and Redondoviridae showed more frequent colonization and higher titers in severe disease. Machine learning analysis demonstrated that integrated features of the microbiome at early sampling points had high power to discriminate ultimate level of COVID-19 MESHD severity. Conclusions: The respiratory tract microbiome and commensal virome are disturbed in COVID-19 MESHD, correlate with systemic immune parameters, and early microbiome features discriminate disease severity. Future studies should address clinical consequences of airway dysbiosis MESHD in COVID-19 MESHD, possible use as biomarkers, and role of bacterial and viral taxa identified here in COVID-19 MESHD pathogenesis.

    Smoking modulates different secretory subpopulations expressing SARS-CoV-2 entry genes in the nasal and bronchial airways

    Authors: Ke Xu; Xingyi Shi; Chris Husted; Rui Hong; Yichen Wang; Boting Ning; Travis Sullivan; Kimberly M Rieger-Christ; Fenghai Duan; Helga Marques; Adam C Gower; Xiaohui Xiao; Hanqiao Liu; Gang Liu; Grant Duclos; Avrum Spira; Sarah A Mazzilli; Ehab Billatos; Marc E Lenburg; Joshua D Campbell; Jennifer Beane

    doi:10.1101/2021.03.30.21254564 Date: 2021-04-04 Source: medRxiv

    Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) is caused by severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), which infects host cells with help from the Viral Entry (VE) proteins ACE2 HGNC, TMPRSS2 HGNC, and CTSL HGNC. Proposed risk factors for viral infection MESHD, as well as the rate of disease progression, include age, sex, chronic obstructive pulmonary disease MESHD, cancer MESHD, and cigarette smoking. To investigate whether the proposed risk factors increase viral infection MESHD by modulation of the VE genes, we examined gene expression profiles of 796 nasal and 1,673 bronchial samples across four lung cancer MESHD screening cohorts containing individuals without COVID-19 MESHD. Smoking was the only clinical factor reproducibly associated with the expression of any VE gene across cohorts. ACE2 HGNC expression was significantly up-regulated with smoking in the bronchus but significantly down-regulated with smoking in the nose. Furthermore, expression of individual VE genes were not correlated between paired nasal and bronchial samples from the same patients. Single-cell RNA-seq of nasal brushings revealed that an ACE2 HGNC gene module was detected in a variety of nasal secretory cells with the highest expression in the C15orf48 HGNC+ secretory cells, while a TMPRSS2 HGNC gene module was most highly expressed in nasal keratinizing epithelial cells. In contrast, single-cell RNA-seq of bronchial brushings revealed that ACE2 HGNC and TMPRSS2 HGNC gene modules were most enriched in MUC5AC HGNC+ bronchial goblet cells. The CTSL HGNC gene module was highly expressed in immune populations of both nasal and bronchial brushings. Deconvolution of bulk RNA-seq showed that the proportion of MUC5AC HGNC+ goblet cells was increased in current smokers in both the nose and bronchus but proportions of nasal keratinizing epithelial cells, C15orf48 HGNC+ secretory cells, and immune cells were not associated with smoking status. The complex association between VE gene expression and smoking in the nasal and bronchial epithelium revealed by our results may partially explain conflicting reports on the association between smoking and SARS-CoV-2 infection MESHD.

    SARS-CoV-2 prevalence and transmission in swimming activities: results from a retrospective cohort study

    Authors: Martin Brink Termansen; Ask Vest Christiansen; Sebastian Frische

    doi:10.1101/2021.03.19.21253351 Date: 2021-03-24 Source: medRxiv

    There is an urgent need for research on the epidemiology of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) causing corona virus disease MESHD 2019 ( COVID-19 MESHD), as the transmissibility differs between settings and populations. Here we report on a questionnaire-based retrospective cohort study of the prevalence and transmission of SARS-CoV-2 among participants in swimming activities in Denmark in the last five months of 2020 during the COVID-19 pandemic MESHD. Eight of 162 swimming activities with a SARS-CoV-2 positive participant led to transmission to 23 other participants. Overall, the percentage of transmission episodes was 4.9% (competitive swimming 8.9%; recreational swimming 1.3%). Overall, the incidence rate of transmission was 19.5 participants per 100.000 pool activity hours (corresponding values: 43.5 and 4.7 for competitive and recreational swimming, respectively). Compliance with precautionary restrictions was highest regarding hand hygiene (98.1%) and lowest in distancing personal sports bags (69.9%). Due to low statistical power, the study showed no significant effect of restrictions. Insight into the risk of transmission of SARS-CoV-2 during indoor swimming is needed to estimate the efficiency of restrictive measures on this and other sports and leisure activities. Only when we know how the virus spreads through various settings, optimal strategies to handle the COVID-19 pandemic MESHD can be developed.

    Antidepressant and antipsychotic drugs reduce viral infection MESHD by SARS-CoV-2 and fluoxetine show antiviral activity against the novel variants in vitro

    Authors: Merve Senem Fred; Suvi Kuivanen; Hasan Ugurlu; Plinio Cabrera Casarotto; Lev Levanov; Kalle Saksela; Olli Vapalahti; Eero Castren

    doi:10.1101/2021.03.22.436379 Date: 2021-03-23 Source: bioRxiv

    Background and Purpose: Repurposing of currently available drugs is a valuable strategy to tackle the consequences of COVID-19 MESHD. Recently, several studies have investigated the effect of psychoactive drugs on SARS-CoV-2 in cell culture models as well as in clinical practice. Our aim was to expand these studies and test some of these compounds against newly emerged variants. Experimental Approach: Several antidepressant drugs and antipsychotic drugs with different primary mechanisms of action were tested in ACE2 HGNC/ TMPRSS2 HGNC-expressing human embryonic kidney cells against the infection by SARS-CoV-2 spike PROTEIN protein-dependent pseudoviruses. Some of these compounds were also tested in human lung epithelial cell line, Calu-1, against the first wave (B.1) lineage of SARS-CoV-2 and the variants of concern, B.1.1.7 and B.1.351. Key Results: Several clinically used antidepressants, including fluoxetine, citalopram, reboxetine, imipramine, as well as antipsychotic compounds chlorpromazine, flupenthixol, and pimozide inhibited the infection by pseudotyped viruses with minimal effects on cell viability. The antiviral action of several of these drugs was verified in Calu-1 cells against the (B.1) lineage of SARS-CoV-2. By contrast, the anticonvulsant carbamazepine, and novel antidepressants ketamine and its derivatives as well as MAO and phosphodiesterase inhibitors phenelzine and rolipram, respectively, showed no activity in the pseudovirus model. Furthermore, fluoxetine remained effective against pseudo viruses with N501Y, K417N, and E484K spike mutations, and the VoC-1 (B.1.1.7) and VoC-2 (B.1.351) variants of SARS-CoV-2. Conclusion and Implications: Our study confirms previous data and extends information on the repurposing of these drugs to counteract SARS-CoV-2 infection MESHD including different variants of concern.

    COVID-19 MESHD Underreporting and its Impact on Vaccination Strategies

    Authors: Vinicius V. L. Albani; Jennifer Loria; Eduardo Massad; Jorge P. Zubelli

    doi:10.1101/2021.03.11.21253404 Date: 2021-03-15 Source: medRxiv

    We present a novel methodology for the stable rate estimation of hospitalization and death related to the Corona Virus Disease MESHD 2019 ( COVID-19 MESHD) using publicly available reports from various distinct communities. These rates are then used to estimate underreported infections on the corresponding areas by making use of reported daily hospitalizations and deaths. The impact of underreporting infections on vaccination strategies is estimated under different disease-transmission scenarios using a Susceptible-Exposed-Infective-Removed-like (SEIR) epidemiological model.

    Differential gene expression by RNA-Seq in Sigma-2 Receptor/ TMEM97 HGNC knockout cells reveals its role in complement activation and SARS-CoV-2 viral uptake

    Authors:

    doi:10.1101/2021.03.14.435180 Date: 2021-03-15 Source: bioRxiv

    Our lab has recently shown that the Sigma-2 Receptor/Transmembrane Protein 97 (sigma- 2R/ TMEM97 HGNC) interacts with the low-density lipoprotein receptor HGNC ( LDLR HGNC) and facilitates the enhanced uptake of various ligands including lipoproteins and intrinsically disordered proteins. TMEM97 HGNC has been recently been shown to interact with severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) viral proteins, highlighting its potential involvement with viral entry into the cell. We hypothesized that sigma-2R/ TMEM97 HGNC may play a role in facilitating viral uptake, and with the regulation of inflammatory and thrombotic MESHD pathways that are involved with viral infection MESHD. In this study, we identified the top differentially expressed genes upon the knockout of sigma-2R/ TMEM97 HGNC, and analyzed the genes involved with the inflammatory and thrombotic MESHD cascades, effects that are observed in patients infected with SARS-CoV-2. We found that the ablation of sigma-2R/ TMEM97 HGNC resulted in an increase in Complement Component MESHD 4 Binding Protein ( C4BP HGNC) proteins, at both the translational and transcriptional levels. We also showed that sigma-2R/ TMEM97 HGNC interacts with the cellular receptor for SARS-CoV-2, the human angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC) receptor, forming a protein complex, and that disruption of this complex results in the inhibition of viral uptake. The results of this study suggest that sigma-2R/ TMEM97 HGNC may be a novel therapeutic target to inhibit SARS- CoV-2 viral uptake, as well as to decrease inflammatory and thrombotic MESHD effects through the modulation of the complement cascade.

    Awake prone position in adult nonintubated patients with acute hypoxaemic respiratory failure MESHD secondary to COVID-19 MESHD:A multi-centre feasibility randomized controlled trial

    Authors: Devachandran Jayakumar; Pratheema Ramachandran; Ebenezer Rabindrarajan; Bharathkumar Tirupakuzhi Vijayaraghavan; Ramakrishnan Nagarajan; Ramesh Venkataraman

    doi:10.1101/2021.03.13.21253499 Date: 2021-03-13 Source: medRxiv

    Background: The primary manifestation of Corona Virus Disease MESHD -2019 ( COVID-19 MESHD) is acute hypoxic respiratory failure MESHD secondary to pneumonia and/or acute respiratory distress syndrome MESHD. Prone position has been shown to improve outcomes in ventilated patients with moderate to severe acute respiratory distress syndrome MESHD. The feasibility and safety of awake prone positioning and its impact on outcomes if any, in non-intubated patients with mild to moderate acute respiratory distress syndrome MESHD secondary to COVID-19 MESHD is unknown. Results of the observational studies published thus far in this pandemic have been conflicting. In this context, we conducted a multi-centre, parallel group, randomised controlled feasibility study on awake prone positioning in non-intubated patients with COVID-19 MESHD pneumonia MESHD requiring supplemental oxygen. Methods: 60 patients diagnosed with acute hypoxic respiratory failure MESHD secondary to COVID -19 pneumonia MESHD requiring 4 or more litres of oxygen to maintain a saturation of [≥] 92% were recruited in this study. Thirty patients each were randomised to either standard care or awake prone group. Patients randomised to the standard care were allowed to change their position as per comfort and patients randomized to the prone group were encouraged to self-prone for at least 6 hours a day. The primary outcome was the proportion of patients adhering to the protocol in each group. Secondary outcomes include failure of therapy leading to escalation of respiratory support, number of hours prone, maximum hours of continuous prone positioning in a day, length of stay in ICU, ICU mortality, total number of patients needing intubation and adverse events. Results: In the prone group, 43% (13 out of 30) of patients were able to self-prone for 6 or more hours a day. The median maximum prone duration per session was 2 hours. In the supine group, 47% (14 out of 30) were completely supine and 53% spent some hours in the prone position, but none exceeded 6 hours. There was no significant difference in any of the secondary outcomes between the two groups and there were no adverse events. Interpretation: Awake proning in non-intubated patients with acute hypoxic respiratory failure MESHD is feasible and safe under clinical trial conditions. The results of our feasibility study will potentially help in the design of larger definitive trials to address this key knowledge gap.

    Mechanism of inhibition of SARS-CoV-2 infection MESHD by the interaction of the spike glycoprotein PROTEIN with heparin

    Authors: Giulia Paiardi; Stefan Richter; Marco Rusnati; Rebecca C Wade

    id:2103.07722v1 Date: 2021-03-13 Source: arXiv

    Heparin is administered intravenously as an anticoagulant to COVID-19 MESHD patients and via aerosol to treat other lung diseases MESHD. It has recently been found to have antiviral activity against SARS-CoV-2 as it hinders attachment of the virus to the host cell by binding to the virus spike glycoprotein PROTEIN. Here, we describe molecular dynamics simulations to investigate how heparin binds to the spike and the mechanism by which it exerts its antiviral activity. The simulations show that heparin polyanionic chains can bind at long, mostly positively charged patches on the spike, preventing the binding of host cell heparan sulphate proteoglycans to the spike. Heparin can mask both the S1/S2 basic motif, thereby inhibiting furin HGNC cleavage and the formation of the prefusion conformation, and the basic residues of the receptor binding domain (RBD), thus acting on the hinge region responsible for the motion of the RBD between inactive closed and active open conformations of the spike. In simulations of the closed spike, heparin binds the RBD and the N-terminal domain of two adjacent spike subunits and hinders the opening. In simulations of the open spike, heparin binds similarly but induces stabilization of the hinge region and a change in RBD motion. Heparin is therefore able to inhibit host cell attachment directly and by two allosteric mechanisms. Furthermore, the simulations provide insights into how heparan sulphate proteoglycans on the host cell can facilitate viral infection MESHD. Our results will aid the rational optimization of heparin derivatives for SARS-CoV-2 antiviral therapy.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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