Targeting invasion strategy of SARS-CoV-2 in bronchial epithelial cells

  • Funded by Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF)
  • Total publications:2 publications

Grant number: 01KI20169A

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Key facts

  • Disease

    COVID-19
  • Start & end year

    2020
    2021
  • Known Financial Commitments (USD)

    $325,081.99
  • Funder

    Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF)
  • Principle Investigator

    Pending
  • Research Location

    Germany, Europe
  • Lead Research Institution

    Technische Universität München
  • Research Category

    Therapeutics research, development and implementation

  • Research Subcategory

    Pre-clinical studies

  • Special Interest Tags

    Gender

  • Study Subject

    Non-Clinical

  • Clinical Trial Details

    N/A

  • Broad Policy Alignment

    Pending

  • Age Group

    Not Applicable

  • Vulnerable Population

    Not applicable

  • Occupations of Interest

    Not applicable

Abstract

Abstract: "COVID19 is caused by the infection of airway epithelial cells and causes severe respiratory collapse that escalates in an overactivation of the immune system. Objectives: To identify the cellular mechanisms in primary epithelial cells in response to SARS-Cov2, the regulation of ACE2, pattern recognition receptors and host defense mechanisms. Further, to investigate the effect of IFN-g and IL-4 on epithelial infection and understand, which epithelial differentiation stages are susceptible to SARS-Cov2. Furthermore, we will investigate the role of potential therapeutic options to inhibit IFN-?-induced ACE2 expression using specific inhibitors for bradykinin-b2 receptor (Icatibant;HOE140), JAK/STAT-pathway (Tofacitinib), FoxO1 (AS1842856), as the ACE2 promoter contains IRF2 and FOXO1 binding sites.Preliminary Results: Primary human epithelial cells can differentiate into type-1 and type-2 epithelial cells affecting large proportions of the functional portfolio. We propose to identify the Sars-Cov2 secretion profile triggered in E1-differentiated cells, which could be used for home-care diagnostic kits, even if the viral origin is unknown. We discovered that ACE2, the SARS-Cov2 entry receptor is strongly up-regulated in the E1 cells. Furthermore, ACE2 protein was found to be higher in E1 cells, while Icatibant, a licensed drug, inhibits ACE2 up-regulation in E1 cells.Outlook: The proposed project sheds light epithelial immune response triggered by SARS-Cov2 in context of the E1 differentiation pathway and offers novel solutions for diagnosis and therapy."; Research Type: discovery; Study population: not applicable

Publicationslinked via Europe PMC

Last Updated:41 minutes ago

View all publications at Europe PMC

Genome-Wide Gene Expression Analysis Reveals Unique Genes Signatures of Epithelial Reorganization in Primary Airway Epithelium Induced by Type-I, -II and -III Interferons.

Early reduction of SARS-CoV-2-replication in bronchial epithelium by kinin B2 receptor antagonism.