Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 295, Issue 52, Pages 18579-18588Publisher
ELSEVIER
DOI: 10.1074/jbc.RA120.015303
Keywords
viral protein; carboxypeptidase; renin angiotensin system; fluorescence resonance energy transfer (FRET); pathogenesis; angiotensin converting enzyme 2; enzymatic activity; SARS-CoV-2 spike protein
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Funding
- Intramural Research Program (IRP) of National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health
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The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has emerged to a pandemic and caused global public health crisis. Human angiotensin-converting enzyme 2(ACE2) was identified as the entry receptor for SARS-CoV-2. As a carboxypeptidase, ACE2 cleaves many biological substrates besides angiotensin II to control vasodilatation and vascular permeability. Given the nanomolar high affinity between ACE2 and SARS-CoV-2 spike protein, we investigated how this interaction would affect the enzymatic activity of ACE2. Surprisingly, SARS-CoV-2 trimeric spike protein increased ACE2 proteolytic activity similar to 3-10 fold against model peptide substrates, such as caspase-1 substrate and Bradykinin-analog. The enhancement in ACE2 enzymatic function was mediated by the binding of SARS-CoV-2 spike RBD domain. These results highlighted the potential for SARS-CoV-2 infection to enhance ACE2 activity, which may be relevant to the cardiovascular symptoms associated with COVID-19.
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