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HGNC Genes

SARS-CoV-2 proteins

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    Topical TMPRSS2 HGNC inhibition prevents SARS-CoV-2 infection MESHD in differentiated primary human airway cells

    Authors: Wenrui Guo; Linsey M Porter; Thomas WM Crozier; Matthew Coates; Akhilesh Jha; Mikel McKie; James A Nathan; Paul J Lehner; Edward JD Greenwood; Frank McCaughan

    doi:10.1101/2021.04.23.440619 Date: 2021-04-23 Source: bioRxiv

    Background: There are no effective prophylactic treatments for SARS-CoV-2 infection MESHD, and limited early treatment options. Viral cell entry requires spike protein PROTEIN binding to the ACE2 HGNC receptor and spike cleavage by TMPRSS2 HGNC, a cell surface serine protease. Targeting of TMPRSS2 HGNC by either androgen blockade or direct inhibition is already in clinical trials in early SARS-CoV-2 infection MESHD. Methods: The likely initial cells of SARS-CoV-2 entry are the ciliated cells of the upper airway. We therefore used differentiated primary human airway epithelial cells maintained at the air-liquid interface (ALI) to test the impact of targeting TMPRSS2 HGNC on the prevention of SARS-CoV-2 infection MESHD. Results: We first modelled the systemic delivery of compounds. Enzalutamide, an oral androgen receptor HGNC antagonist, had no impact on SARS-Cov-2 infection MESHD. By contrast, camostat mesylate, an orally available serine protease inhibitor, blocked SARS-CoV-2 entry. However, camostat is rapidly metabolised in the circulation in vivo, and systemic bioavailability after oral dosing is low. We therefore modelled local airway administration by applying camostat to the apical surface of the differentiated ALI cultures. We demonstrated that a brief exposure to topical camostat is effective at restricting SARS-CoV-2 viral infection MESHD. Conclusion: These experiments demonstrate a potential therapeutic role for topical camostat for pre- or post-exposure prophylaxis of SARS-CoV-2, which can now be evaluated in a clinical trial.

    Enzalutamide, a prostate cancer MESHD therapeutic, downregulates TMPRSS2 HGNC in lung and reduces cellular entry of SARS-CoV-2

    Authors: D. A. Leach; A. Mohr; E. S. Giotis; A. M. Isac; L. L. Yates; W. S. Barclay; R. M. Zwacka; C. L. Bevan; G. N. Brooke

    doi:10.21203/rs.3.rs-137931/v1 Date: 2020-12-29 Source: ResearchSquare

    The COVID-19 pandemic MESHD, caused by the novel human coronavirus SARS-CoV-2 coronavirus MESHD, attacks various organs but most destructively the lung. It has been shown that SARS-CoV-2 entry into lung cells requires two host cell surface proteins: ACE2 HGNC and TMPRSS2 HGNC. Downregulation of one or both of these is thus a potential therapeutic approach for COVID-19 MESHD TMPRSS2 HGNC is a known target of the androgen receptor HGNC, a ligand-activated transcription factor; activation of the androgen receptor HGNC increases TMPRSS2 HGNC levels in various tissues, most notably the prostate. We show here that treatment with the antiandrogen enzalutamide – a well-tolerated drug widely used in advanced prostate cancer MESHD – reduces TMPRSS2 HGNC levels in human lung cells. Further, enzalutamide treatment of mice dramatically decreased Tmprss2 levels in the lung. To determine therapeutic potential, we assessed uptake of SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN protein pseudotyped lentivirus and live SARS-CoV-2 into human lung cells and saw a significant reduction in viral entry and infection upon treatment with the antiandrogens enzalutamide and bicalutamide. In support of this new experimental data, analysis of existing datasets shows striking co-expression of AR and TMPRSS2 HGNC, including in specific lung cell types that are targeted by SARS-CoV-2. Together, the data presented provides strong evidence to support clinical trials to assess the efficacy of antiandrogens as a treatment option for COVID-19 MESHD.

    Identifying pathways and networks associated with the SARS-CoV-2 cell receptor ACE2 HGNC based on gene expression profiles in human tissues

    Authors: Qiushi Feng; Lin Li; Xiaosheng Wang

    doi:10.21203/rs.3.rs-34488/v1 Date: 2020-06-09 Source: ResearchSquare

    The angiotensin-converting enzyme 2 ( ACE2 HGNC) is a host cell receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has infected more than six million people worldwide and has caused more than 370,000 deaths as of May 31, 2020. An investigation of ACE2 HGNC expression in human tissues may provide insights into the mechanism of SARS-CoV-2 infection MESHD. We identified pathways associated with ACE2 HGNC expression and gene co-expression networks of ACE2 HGNC in pan-tissue based on the gene expression profiles in human tissues. We found that the pathways significantly associated with ACE2 HGNC upregulation were mainly involved in immune, stromal signature, metabolism, cell growth and proliferation, and cancer MESHD and other diseases. The number of genes having a significant positive expression correlation with ACE2 HGNC in females far exceeded that in males. The estrogen receptors ( ESR1 HGNC and ESR2 HGNC) and androgen receptor HGNC (AR) genes had a significant positive expression correlation with ACE2 HGNC in pan-tissue. Meanwhile, the enrichment levels of immune cells were positively associated with the expression levels of ESR1 HGNC and ESR2 HGNC, while they were inversely associated with the expression levels of AR in pan-tissue and in multiple individual tissues. It suggests that females are likely to have a more robust immune defense system against SARS-CoV-2 than males, partially explaining why females have better clinical outcomes of SARS-CoV-2 infections MESHD than males. Our data warrant further investigation for understanding the mechanism of SARS-CoV-2 infection MESHD.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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