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HGNC Genes

SARS-CoV-2 proteins

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    Suppression of miR-155 HGNC attenuates lung cytokine storm induced by SARS-CoV-2 infection MESHD in human ACE2 HGNC-transgenic mice

    Authors: Dharmendra Kumar Soni; Juan Cabrera-Luque; Swagata Kar; Chaitali Sen; Joseph Devaney; Roopa Biswas; Laura Chegwidden; Siang Ing Lee; Lennard YW Lee; David J Pinato; Gino M Dettorre; Claire Palles; Yamir Moreno; Esteban Moro; Bianca Magro; Gianpaolo Mangia; Ferdinando L. Lorini; Giulio Guagliumi; Stefano Fagiuoli; Gianfranco Parati; Michele Senni; Hans Pargger; Diana Ciardo; Olivier Dubuis; Andreas Buser; Sarah Tschudin-Sutter; Manuel Battegay; Rita Schneider-Sliwa; Karsten M. Borgwardt; Hans H. Hirsch; Adrian Egli

    doi:10.1101/2020.12.17.423130 Date: 2020-12-17 Source: bioRxiv

    Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is a recent global pandemic. It is a deadly human viral disease, caused by the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), with a high rate of infection, morbidity and mortality. Therefore, there is a great urgency to develop new therapies to control, treat and prevent this disease. Endogenous microRNAs (miRNAs, miRs) of the viral host are key molecules in preventing viral entry and replication, and building an antiviral cellular defense. Here, we have analyzed the role of miR-155, one of the most powerful drivers of host antiviral responses including immune and inflammatory responses, in the pathogenicity of SARS-CoV-2 infection MESHD. Subsequently, we have analyzed the potency of anti-miR-155 therapy in a COVID-19 MESHD mouse model (mice transgenic for human angiotensin I- converting enzyme 2 receptor (tg-mice hACE2 HGNC)). We report for the first time that miR-155 HGNC expression is elevated in COVID-19 MESHD patients. Further, our data indicate that the viral load as well as miR-155 HGNC levels are higher in male relative to female patients. Moreover, we find that the delivery of anti-miR-155 to SARS-CoV-2-infected MESHD tg-mice hACE2 HGNC effectively suppresses miR-155 expression, and leads to improved survival and clinical scores. Importantly, anti-miR-155-treated tg-mice hACE2 HGNC infected with SARS-CoV-2 not only exhibit reduced levels of pro-inflammatory cytokines, but also have increased anti-viral and anti-inflammatory cytokine responses in the lungs. Thus, our study suggests anti-miR-155 as a novel therapy for mitigating the lung cytokine storm induced by SARS-CoV-2 infection MESHD.

    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.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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