Corpus overview


Overview

MeSH Disease

HGNC Genes

Transmission

gender (1)


Seroprevalence

antibody (1)

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    Recombinant ACE2 HGNC Expression is Required for SARS-CoV-2 to Infect Primary Human Endothelial Cells and Induce Inflammatory and Procoagulative Responses

    Authors: Jonas Nascimento Conde; William R. Schutt; Elena Gorbunova; Erich R. Mackow; Suprabhat Mukherjee; Kianna M. Nguyen; Ming H. Ho; Jung-Eun Shin; Jared Feldman; Blake M. Hauser; Timothy M. Caradonna; Laura M. Wingler; Aaron G. Schmidt; Debora S. Marks; Jonathan Abraham; Andrew C. Kruse; Chang C. Liu

    doi:10.1101/2020.11.10.377606 Date: 2020-11-11 Source: bioRxiv

    SARS-CoV-2 causes COVID-19 MESHD, an acute respiratory distress HP respiratory distress MESHD syndrome ( ARDS MESHD) characterized by pulmonary edema HP pulmonary edema MESHD, viral pneumonia MESHD pneumonia HP, multiorgan dysfunction, coagulopathy and inflammation MESHD. SARS-CoV-2 uses angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC) receptors to infect and damage ciliated epithelial cells in the upper respiratory tract. In alveoli, gas exchange occurs across an epithelial-endothelial barrier that ties respiration to endothelial cell (EC) regulation of edema HP edema MESHD, coagulation MESHD and inflammation MESHD. How SARS-CoV-2 dysregulates MESHD vascular functions to cause ARDS MESHD in COVID-19 MESHD patients remains an enigma focused on dysregulated EC responses. Whether SARS-CoV-2 directly or indirectly affects functions of the endothelium remains to be resolved and critical to understanding SARS-CoV-2 pathogenesis and therapeutic targets. We demonstrate that primary human ECs lack ACE2 HGNC receptors at protein and RNA levels, and that SARS-CoV-2 is incapable of directly infecting ECs derived from pulmonary, cardiac, brain, umbilical vein or kidney tissues. In contrast, pulmonary ECs transduced with recombinant ACE2 HGNC receptors are infected by SARS-CoV-2 and result in high viral titers (~1x107/ml), multinucleate syncytia MESHD and EC lysis. SARS-CoV-2 infection MESHD of ACE2 HGNC-expressing ECs elicits procoagulative and inflammatory responses observed in COVID-19 MESHD patients. The inability of SARS-CoV-2 to directly infect and lyse ECs without ACE2 HGNC expression explains the lack of vascular hemorrhage MESHD in COVID-19 MESHD patients and indicates that the endothelium is not a primary target of SARS-CoV-2 infection MESHD. These findings are consistent with SARS-CoV-2 indirectly activating EC programs that regulate thrombosis MESHD and endotheliitis MESHD in COVID-19 MESHD patients, and focus strategies on therapeutically targeting epithelial and inflammatory responses that activate the endothelium or initiate limited ACE2 HGNC independent EC infection MESHD.

    Hypothesis: mPGES-1-Derived Prostaglandin E2, a So Far Missing Link in COVID-19 MESHD 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 MESHD (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 MESHD 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 MESHD pathophysiology. Based on this we suggest measuring PGE2 in patients and evaluating selective inhibition of the human microsomal prostaglandin E synthase-1 HGNC (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.

    Functional pangenome analysis provides insights into the origin, function and pathways to therapy of SARS-CoV-2 coronavirus MESHD

    Authors: Intikhab Alam; Allan K Kamau; Maxat Kulmanov; Stefan T Arold; Arnab T Pain; Takashi Gojobori; Carlos M. Duarte

    doi:10.1101/2020.02.17.952895 Date: 2020-02-21 Source: bioRxiv

    The spread of the novel coronavirus (SARS-CoV-2) has triggered a global emergency, that demands urgent solutions for detection and therapy to prevent escalating health, social and economic impacts. The spike protein (S) of this virus enables binding to the human receptor ACE2 HGNC, and hence presents a prime target for vaccines preventing viral entry into host cells1. The S proteins from SARS-CoV-1 and SARS-CoV-2 MESHD are similar2, but structural differences in the receptor binding domain (RBD) preclude the use of SARS-CoV-1-specific neutralizing antibodies SERO to inhibit SARS-CoV-23. Here we used comparative pangenomic analysis of all sequenced Betacoronaviruses to reveal that, among all core gene clusters present in these viruses, the envelope protein E shows a variant shared by SARS and SARS-Cov2 with two completely-conserved key functional features, an ion-channel and a PDZ-binding Motif (PBM). These features trigger a cytokine storm that activates the inflammasome, leading to increased edema HP edema MESHD in lungs causing the acute respiratory distress syndrome MESHD respiratory distress HP syndrome ( ARDS MESHD)4-6, the leading cause of death MESHD in SARS-CoV-1 and SARS-CoV-2 infection7 MESHD SARS-CoV-2 infection MESHD7,8. However, three drugs approved for human use may inhibit SARS-CoV-1 and SARS-CoV-2 Protein E, either acting upon the ion channel (Amantadine and Hexamethylene amiloride9,10) or the PBM (SB2035805), thereby potentially increasing the survival of the host, as already demonstrated for SARS-CoV-1in animal models. Hence, blocking the SARS protein E inhibits development of ARDS in vivo. Given that our results demonstrate that the protein E subcluster for the SARS clade is quasi-identical for the key functional regions of SARS-CoV-1 and SARS-CoV-2, we conclude that use of approved drugs shown to act as SARS E protein inhibitors can help prevent further casualties from COVID-2019 while vaccines and other preventive measures are being developed.

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