Modulation of SARS-CoV-2 Spike protein function by ADAM family proteases (MoCoSpA)
- Funded by Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF)
- Total publications:2 publications
Grant number: 01KI20207
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Key facts
Disease
COVID-19Start & end year
20202021Known Financial Commitments (USD)
$231,146.99Funder
Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF)Principal Investigator
Prof. Andreas LudwigResearch Location
GermanyLead Research Institution
RWTH Aachen UniversityResearch Priority Alignment
N/A
Research Category
Pathogen: natural history, transmission and diagnostics
Research Subcategory
Pathogen morphology, shedding & natural history
Special Interest Tags
N/A
Study Type
Clinical
Clinical Trial Details
N/A
Broad Policy Alignment
Pending
Age Group
Unspecified
Vulnerable Population
Unspecified
Occupations of Interest
Unspecified
Abstract
The SARS-CoV-2 spike protein interacts with angiotensin converting enzyme 2 (ACE-2) on epithelial cells in the lung which is a crucial step in viral infection and development of COVID2019. We propose that the metalloproteinases ADAM10 and ADAM17 are critical modulators of SARS-CoV-2 spike protein interaction with its receptor ACE-2 on lung epithelial cells. We want to study the induced release and functions of shed ACE-2 which may act as a soluble competitor and reduce the interaction of the virus with its membrane-anchored ACE-2 receptor. Moreover we want to study whether the spike protein triggers an inflammatory response by provoking increased ADAM-mediated shedding of proinflammatory mediators. These questions will be addressed in parallel by exposure of cultured epithelial cell lines and primary cells exposure to SARS-CoV-2 spike protein as well as by analysis of COVID19 patient tissues. For the analysis we will use established procedures to study ADAM activity, binding of adapter molecules, release of shed ACE-2, quantification of shed inflammatory mediators and cleavage of adhesion molecules. The analysis of these ADAM17 dependent responses shall help to understand why SARS-CoV-2 infection can cause a severe inflammatory response leading to ARDS with high mortality.
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