High affinity binding of SARS-CoV-2 spike protein enhances ACE2 carboxypeptidase activity.

The Journal of Biological Chemistry
Jinghua Lu, Peter D Sun


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 ∼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.


Jan 1, 1989·Advances in Experimental Medicine and Biology·I A Sheikh, A P Kaplan
Oct 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·C Chavkin, A Goldstein
Aug 30, 2000·Pain·R M Caudle, A J Mannes
Jan 30, 2002·The Journal of Biological Chemistry·Chad VickersPeter Tummino
Feb 3, 2004·The Journal of Biological Chemistry·Paul TowlerMichael W Pantoliano
Apr 28, 2004·Trends in Endocrinology and Metabolism : TEM·Louise M BurrellMark E Cooper
Jul 8, 2005·Nature·Yumiko ImaiJosef M Penninger
Sep 5, 2008·American Journal of Physiology. Cell Physiology·Patricia E GallagherE Ann Tallant
Feb 11, 2014·Current Hypertension Reports·Jasmina VaragicCarlos M Ferrario
Jan 25, 2020·The New England Journal of Medicine·Na ZhuUNKNOWN China Novel Coronavirus Investigating and Research Team
Feb 23, 2020·Science·Daniel WrappJason S McLellan
Feb 23, 2020·The Lancet. Respiratory Medicine·Zhe XuFu-Sheng Wang
Apr 1, 2020·Nature·Jian ShangFang Li
May 7, 2020·Annals of Internal Medicine·Dominic WichmannStefan Kluge
Jun 9, 2020·MedRxiv : the Preprint Server for Health Sciences·Bruna Gg PintoHelder I Nakaya

❮ Previous
Next ❯


Mar 4, 2021·The Journal of Physical Chemistry. B·Billy J Williams-NoonanIrene Yarovsky

❮ Previous
Next ❯

Datasets Mentioned


Methods Mentioned

size exclusion chromatography

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.