Corpus overview


Overview

MeSH Disease

Human Phenotype

Transmission

Seroprevalence
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    SARS-CoV-2 Infections - Gene Expression Omnibus (GEO) Data Mining, Pathway Enrichment Analysis, and Prediction of Repurposable Drugs/Compounds

    Authors: Srilakshmi Chaparala; Carrie L Iwema; Ansuman Chattopadhyay

    id:10.20944/preprints202009.0459.v1 Date: 2020-09-19 Source: Preprints.org

    The COVID-19 global pandemic has created dire consequences with an alarming rate of morbidity and mortality. There are not yet vaccine or efficacious treatment options to combat the causative SARS-CoV-2 infection MESHD. This paper describes the identification of potentially repurposable drugs for COVID-19 treatment by conducting pathway enrichment analysis on publicly available Gene Expression Omnibus datasets. We first determined SARS-CoV-2 infection MESHD-induced alterations of host gene expressions and pathways. We then identified drugs or compounds that target and counter virus-triggered cellular perturbations, suggesting their potential repurposing for COVID-19 treatment. The key findings are that SARS-CoV-2 infection MESHD in host cells induces mitochondrial dysfunction MESHD, inhibits oxidative phosphorylation, and activates several immune response and pro-inflammatory pathways. Triptolide, the major bioactive component of a traditional Chinese medicine herb, may rescue mitochondrial dysfunction MESHD by activating oxidative phosphorylation. Further in vitro and in vivo studies are necessary to verify these results prior to clinical application.

    Mitochondrial induced T cell apoptosis and aberrant myeloid metabolic programs define distinct immune cell subsets during acute and recovered SARS-CoV-2 infection MESHD

    Authors: Elizabeth Thompson; Katherine Cascino; Alvaro Ordonez; Weiqiang Zhou; Ajay Vaghasia; Anne Hamacher-Brady; Nathan Brady; Im-Hong Sun; Rulin Wang; Avi Rosenberg; Michael Delanoy; Richard Eric Rothman; Katherine Fenstermacher; Lauren Sauer; Kathryn Shaw-Saliba; Evan M Bloch; Andrew Redd; Aaron AR Tobian; Maureen Horton; Kellie Smith; Andrew Pekosz; Franco D'Alessio; Srinivasan Yegnasubramanian; Honkai Ji; Andrea L Cox; Jonathan D Powell

    doi:10.1101/2020.09.10.20186064 Date: 2020-09-11 Source: medRxiv

    By interrogating metabolic programs in the peripheral blood SERO mononuclear cells (PBMC) of acutely infected COVID-19 patients, we identified novel and distinct immune cell subsets Our studies identified a non-clonal population of T cells expressing high H3K27me3 and voltage-dependent anion channel (VDAC) with mitochondrial dysfunction MESHD and increased susceptibility to cell death. Characterized by dysmorphic mitochondria and increased cytoplasmic cytochrome c, apoptosis of these cells was inhibited by preventing VDAC aggregation or blocking caspase activation. Further, we observed a marked increase in Hexokinase II+ polymorphonuclear-myeloid derived suppressor cells (PMN-MDSC). While PMN-MDSC were also found in the PBMC of patients with other viral infections MESHD, the Hexokinase II+ PMN-MDSC were found exclusively in the acute COVID-19 patients with moderate or severe disease. Finally, we identified a population of monocytic MDSC (M-MDSC) expressing high carnitine palmitoyltransferase I (CPT1a) and VDAC, which were present in the PBMC of the acute COVID-19 patients, but not recovered COVID-19 patients and whose presence correlated with severity of disease. Overall, these unique populations of immune cells provide insight into the pathogenesis of SARS-CoV-2 infection MESHD and provide a means to predict and track disease severity as well as an opportunity to design and evaluate novel therapeutic regimens.

    Proteins Nsp12 and 13 of SARS-CoV-2 Have Mitochondrial Recognition Signal: A Connection with Cellular Mitochondrial Dysfunction and Disease Manifestation MESHD

    Authors: Upasana Ray; Feroza Begum

    id:10.20944/preprints202006.0352.v1 Date: 2020-06-29 Source: Preprints.org

    Mitochondria are classically termed as powerhouse of a mammalian cell. Most of the cellular chemical energy in the form of adenosine tri phosphate (ATP) is generated by mitochondria and dysregulation of mitochondrial functions thus can be potentially fatal of cellular homeostasis and health. Acute respiratory distress HP has been earlier linked to mitochondrial dysfunction MESHD. SARS-CoV-2 infection MESHD severity leads to acute respiratory distress HP respiratory distress MESHD syndrome ( ARDS MESHD) and can be fatal. We tried to investigate possible connection between SARS-CoV-2, ARDS and mitochondria. Here, we report identification of SARS-CoV-2 non-structural proteins (particularly Nsp12 and 13) that have recognition sequence with respect to mitochondrial entry. We also report that these proteins can potentially shuttle between cytoplasm and mitochondria based on the localization signals and help in downstream maintenance of the virus. Their properties to use ATP for enzymatic activities may cause ATP scavenging allowing viral RNA functions in lieu of host cell health.

    COVID-19 and Crosstalk With the Hallmarks of Aging

    Authors: Shabnam Salimi; John M. Hamlyn

    id:10.20944/preprints202004.0182.v2 Date: 2020-05-16 Source: Preprints.org

    Within the past several decades, the emergence of new viral diseases MESHD with severe health complications and mortality is evidence of an age TRANS-dependent, compromised bodily response to abrupt stress with concomitantly reduced immunity. The new severe acute respiratory syndrome coronavirus 2 MESHD, SARS-CoV-2, causes coronavirus disease MESHD 2019 (COVID-19). It has increased morbidity and mortality in persons with underlying chronic diseases MESHD and those with a compromised immune system regardless of age TRANS and in older adults TRANS who are more likely to have these conditions. While SARS-CoV-2 is highly virulent, there is variability in the severity of the disease and its complications in humans. Severe pneumonia HP pneumonia MESHD, acute respiratory distress syndrome MESHD respiratory distress HP syndrome, lung fibrosis MESHD, cardiovascular events, acute kidney injury HP acute kidney injury MESHD, stroke HP stroke MESHD, hospitalization, and mortality have been reported that result from pathogen–host interactions. Hallmarks of aging, interacting with one another, have been proposed to influence health span in older adults TRANS, possibly via mechanisms regulating the immune system. Here, we review the potential roles of the hallmarks of aging coupled with host–coronavirus interactions. Of these hallmarks, we focused on those that directly or indirectly interact with viral infections MESHD, including immunosenescence, inflammation MESHD and inflammasomes, adaptive immunosenescence, genomic instability, mitochondrial dysfunction MESHD, telomere attrition, epigenetic alterations, and impaired autophagy. These hallmarks likely contribute to the increased pathophysiological responses to SARS-CoV-2 among older adults TRANS and may play roles as an additive risk of accelerated biological aging even after recovery. We also briefly discuss the role of anti-aging drug candidates that require paramount attention in COVID-19 research.

    Lung biopsy cells transcriptional landscape from COVID-19 patient stratified lung injury MESHD in SARS-CoV-2 infection through impaired pulmonary surfactant metabolism

    Authors: Abul B.M.M.K. Islam; Md. Abdullah-Al-Kamran Khan

    doi:10.1101/2020.05.07.082297 Date: 2020-05-08 Source: bioRxiv

    Clinical management of COVID-19 is still complicated due to the lack of therapeutic interventions to reduce the breathing problems, respiratory complications MESHD and acute lung injury MESHD - which are the major complications of most of the mild to critically affected patients and the molecular mechanisms behind these clinical features are still largely unknown. In this study, we have used the RNA-seq gene expression pattern in the COVID-19 affected lung biopsy cells and compared it with the effects observed in typical cell lines infected with SARS-CoV-2 and SARS-CoV MESHD. We performed functional overrepresentation analyses using these differentially expressed genes to signify the processes/pathways which could be deregulated during SARS-CoV-2 infection MESHD resulting in the symptomatic impairments observed in COVID-19. Our results showed that the significantly altered processes include inflammatory responses, antiviral cytokine signaling, interferon responses, and interleukin signaling etc. along with downmodulated processes related to lungs functionality like-responses to hypoxia MESHD, lung development, respiratory processes, cholesterol biosynthesis and surfactant metabolism. We also found that the viral protein interacting hosts proteins involved in similar pathways like: respiratory failure HP respiratory failure MESHD, lung diseases MESHD, asthma HP asthma MESHD, and hypoxia MESHD responses etc., suggesting viral proteins might be deregulating the processes related to acute lung injury MESHD/breathing complications in COVID-19 patients. Protein-protein interaction networks of these processes and map of gene expression of deregulated genes revealed that several viral proteins can directly or indirectly modulate the host genes/proteins of those lung related processes along with several host transcription factors and miRNAs. Surfactant proteins and their regulators SPD, SPC, TTF1 etc. which maintains the stability of the pulmonary tissue are found to be downregulated through viral NSP5, NSP12 that could lead to deficient gaseous exchange by the surface films. Mitochondrial dysfunction MESHD owing to the aberration of NDUFA10, NDUFAF5, SAMM50 etc. by NSP12; abnormal thrombosis HP abnormal thrombosis MESHD in lungs through atypical PLAT, EGR1 functions by viral ORF8, NSP12; dulled hypoxia MESHD responses due to unusual shift in HIF-1 downstream signaling might be the causative elements behind the acute lung injury MESHD in COVID-19 patients. Our study put forward a distinct mechanism of probable virus induced lung damage MESHD apart from cytokine storm and advocate the need of further research for alternate therapy in this direction.

    Hypothesis: mPGES-1-Derived Prostaglandin E2, a So Far Missing Link in COVID-19 Pathophysiology?

    Authors: Jan Smeitink; Xiaolan Jiang; Svetlana Pecheritsyna; Herma Renkema; Rob van Maanen; Julien Beyrath

    id:10.20944/preprints202004.0180.v1 Date: 2020-04-12 Source: Preprints.org

    With frequencies varying up to 20%, treatment resistant pulmonary failure MESHD is a major life-threatening complication in COVID-19 (SARS-CoV-2, HCoV19) disease pathology. Both acute respiratory distress syndrome MESHD respiratory distress HP syndrome ( ARDS MESHD), proposed to be caused by an over-reacting immune system which floods the lung with edema HP edema MESHD, a liquid consisting of inflammatory cells, and diminished lung perfusion, have been postulated to cause this treatment resistant lung failure MESHD. Aging, co-morbidities, male TRANS gender TRANS and obesity HP obesity MESHD are pre-existing factors associated with the more severe outcome. Thrombosis MESHD is more frequently observed than usually seen during ICU admission. Different hypotheses explaining the pathophysiological cascade leading to fast progressing severe COVID-19 disease and how to counteract it have been proposed. A variety of intervention studies to control severity are ongoing or planned. Not suggested so far, we here hypothesize that the inflammatory lipid modulator prostaglandin E2 (PGE2) executes a prominent role in COVID-19 pathophysiology. Based on this we suggest measuring PGE2 in patients and evaluating selective inhibition of the human microsomal prostaglandin E synthase-1 (mPGES-1) as a potential innovative therapeutic approach in this devastating condition for which sonlicromanol, a drug currently in phase 2b studies for mitochondrial disease MESHD, is a candidate.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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