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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

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    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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