RT Journal Article
SR Electronic
T1 High affinity binding of SARS-CoV-2 spike protein enhances ACE2 carboxypeptidase activity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.01.182659
DO 10.1101/2020.07.01.182659
A1 Jinghua Lu
A1 Peter D. Sun
YR 2020
UL http://biorxiv.org/content/early/2020/07/01/2020.07.01.182659.abstract
AB A novel coronavirus (SARS-CoV-2) has emerged to a global pandemic and caused significant damages to public health. 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 Ang II to control vasodilatation and permeability. Given the nanomolar high affinity between ACE2 and SARS-CoV-2 spike protein, we wonder how this interaction would affect the enzymatic activity of ACE2. Surprisingly, SARS-CoV-2 trimeric spike protein increased ACE2 proteolytic activity ~3-10 fold when fluorogenic caspase-1 substrate and Bradykinin-analog peptides were used to characterize ACE2 activity. In addition, the enhancement was mediated by ACE2 binding of RBD domain of SARS-CoV-2 spike. These results highlighted the altered activity of ACE2 during SARS-CoV-2 infection and would shed new lights on the pathogenesis of COVID-19 and its complications for better treatments.Competing Interest StatementThe authors have declared no competing interest.