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HGNC Genes

SARS-CoV-2 proteins

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    Oral Hsp90 HGNC inhibitor, SNX-5422, attenuates SARS-CoV-2 replication and dampens inflammation MESHD in airway cells.

    Authors: Ria Goswami; Veronica S. Russell; Joshua J. Tu; Philip Hughes; Francine Kelly; Stephanie N. Langel; Justin Steppe; Scott M. Palmer; Timothy Haystead; Maria Blasi; Sallie R. Permar

    doi:10.1101/2021.02.23.432479 Date: 2021-02-23 Source: bioRxiv

    Currently available SARS-CoV-2 therapeutics are targeted towards moderately to severely ill patients and require intravenous infusions, with limited options for exposed or infected MESHD patients with no or mild symptoms. While vaccines have demonstrated protective efficacy, vaccine hesitancy and logistical distribution challenges will delay their ability to end the pandemic. Hence, there is a need for rapidly translatable, easy-to-administer-therapeutics, that can prevent SARS-CoV-2 disease progression, when administered in the early stages of infection. We demonstrate that an orally bioavailable Hsp90 HGNC inhibitor, SNX-5422, currently in clinical trials as an anti-cancer therapeutic, inhibits SARS-CoV-2 replication in vitro at a high selectivity index. SNX-5422 treatment of human primary airway epithelial cells dampened expression of inflammatory pathways associated with poor SARS-CoV-2 disease MESHD outcomes. Additionally, SNX-5422 interrupted expression of host factors that are crucial for SARS-CoV-2 replication machinery. Development of SNX-5422 as SARS-CoV-2-early-therapy will dampen disease severity, resulting in better clinical outcomes and reduced hospitalizations.

    A Connectivity Map-Based Drug Repurposing Study and Integrative Analysis of Transcriptomic Profiling of SARS-CoV-2 Infection MESHD

    Authors: seyedeh zahra mousavi; mojdeh rahmanian; ashkan sami

    doi:10.26434/chemrxiv.12469316.v1 Date: 2020-06-15 Source: ChemRxiv

    Aims: The recent outbreak of COVID-19 MESHD has become a global health concern. There are currently no effective treatment strategies and vaccines for the treatment or prevention of this fatal disease. The current study aims to determine promising treatment options for the COVID-19 MESHD through a computational drug repurposing approach.Materials and methods: In this study, we focus on differentially expressed genes (DEGs), detected in SARS-CoV-2 infected MESHD cell lines including “the primary human lung epithelial cell line NHBE” and “the transformed lung alveolar MESHD cell line A549”. Next, the identified DEGs are used in the connectivity map ( CMap HGNC) analysis to identify similarly acting therapeutic candidates. Furthermore, to interpret lists of DEGs, pathway enrichment and protein network analysis are performed. Genes are categorized into easily interpretable pathways based on their biological functions, and overrepresentations of each pathway are tested in comparison to what is expected randomly.Key findings: The results suggest the effectiveness of Saquinavir, lansoprazole, folic acid, ebselen, aminocaproic acid, simvastatin, surfactant stimulant drugs, heat shock protein 90 ( HSP90 HGNC) inhibitors, histone deacetylase (HDAC) inhibitors, metronidazole, inhaled corticosteroids (ICS) and many other clinically approved drugs and investigational compounds as potent drugs against COVID-19 MESHD outbreak.Significance: Making new drugs remain a lengthy process, so the drug repurposing approach provides an insight into the therapeutics that might be helpful in this pandemic. In this study, pathway enrichment and protein network analysis are also performed, and the effectiveness of some drugs obtained from the CMap HGNC analysis has been investigated according to previous research.

    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.

    Drug Repositioning Suggests a Role for the Heat Shock Protein 90 Inhibitor Geldanamycin in Treating COVID-19 MESHD Infection

    Authors: Iyad Sultan; Scott Howard; Abdelghani Tbakhi

    doi:10.21203/rs.3.rs-18714/v1 Date: 2020-03-20 Source: ResearchSquare

    Drug repositioning offers an unmatched opportunity to offer novel therapeutics to treat SARS family of coronaviruses ( SARS-FCoVs MESHD); an issue that became extremely urgent with the spreading of a novel virus with potential to threaten the lives of millions of people. Hereby, we analyzed a dataset of patients who presented with SARS during the 2003 outbreak. We established a gene signature that defines differential gene expression in patients who were sick with SARS vs. healthy controls and convalescent patients. We used a robust platform to conduct drug repositioning based on clustered gene expression and pathway enrichment to identify best matching drugs. We identified 55 agents of potential benefit. In most of these drugs we were able to establish a link to previous related research, use as antiviral, or at least a hypothetical role in treating SARS-FCoVs MESHD. Most notably, the heat shock protein 90 ( hsp90 HGNC) emerged as a major component that enables viruses to hijack infected cells through the process of autophagy. Almost half of the drugs identified could be linked to hsp90 HGNC. As such, we propose using hsp90 HGNC inhibitors, mainly geldanamycin and its derivatives, to treat COVID-19 MESHD.

The ZB MED preprint Viewer preVIEW includes all COVID-19 related preprints from medRxiv and bioRxiv, from ChemRxiv, from ResearchSquare, from arXiv and from Preprints.org and is updated on a daily basis (7am CET/CEST).
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MeSH Disease
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SARS-CoV-2 Proteins


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