Targeting protease-mediated activation of SARS-CoV-2

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

Grant number: 01KI20135

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Key facts

  • Disease

    COVID-19
  • Start & end year

    2020
    2021
  • Known Financial Commitments (USD)

    $410,586.36
  • Funder

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

    Pending
  • Research Location

    Germany, Europe
  • Lead Research Institution

    Universitätsklinikum Ulm
  • Research Category

    Pathogen: natural history, transmission and diagnostics

  • Research Subcategory

    Pathogen genomics, mutations and adaptations

  • 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

discovery - Here, I propose to decipher the role of furin and related proteases in the activation of SARS-CoV-2 spike proteins. We will compare evolutionarily diverse coronaviruses to characterize proteolytic spike maturation and the downstream effects on viral infectivity. Taking advantage of our long-standing expertise in host-virus co-evolution, we will also characterize spike mutations that emerge during the current SARS-CoV-2 pandemic and may confer a selection advantage to the virus as they enhance furin-mediated cleavage. Notably, we previously identified a novel mechanism of antiviral immunity, demonstrating that guanylate-binding proteins 2 and 5 (GBP2/5) restrict a variety of viruses by targeting furin. We hypothesize that this mechanism also suppresses replication of SARS-CoV-2. In a translational approach, we will therefore test whether induction of GBP2/5 and/or inhibition of furin can limit the spread of SARS-CoV 2. The proposed project will not only provide important insights into the determinants of SARS-CoV-2 infectivity and tropism, but also help to assess consequences of mutations emerging during the current outbreak and might identify promising targets for therapeutic intervention.

Publicationslinked via Europe PMC

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ORF3c is expressed in SARS-CoV-2-infected cells and inhibits innate sensing by targeting MAVS.

Evolutionary conflicts and adverse effects of antiviral factors.