SARS-CoV-2 spike protein binding selectively accelerates substrate-specific catalytic activity of ACE2

J Biochem. 2021 Oct 11;170(2):299-306. doi: 10.1093/jb/mvab041.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that has given rise to the devastating global pandemic. In most cases, SARS-CoV-2 infection results in the development of viral pneumonia and acute respiratory distress syndrome, known as 'coronavirus disease 2019' or COVID-19. Intriguingly, besides the respiratory tract, COVID-19 affects other organs and systems of the human body. COVID-19 patients with pre-existing cardiovascular disease have a higher risk of death, and SARS-CoV-2 infection itself may cause myocardial inflammation and injury. One possible explanation of such phenomena is the fact that SARS-CoV-2 utilizes angiotensin-converting enzyme 2 (ACE2) as the receptor required for viral entry. ACE2 is expressed in the cells of many organs, including the heart. ACE2 functions as a carboxypeptidase that can cleave several endogenous substrates, including angiotensin II, thus regulating blood pressure and vascular tone. It remains largely unknown if the SARS-CoV-2 infection alters the enzymatic properties of ACE2, thereby contributing to cardiovascular complications in patients with COVID-19. Here, we demonstrate that ACE2 cleavage of des-Arg9-bradykinin substrate analogue is markedly accelerated, while cleavage of angiotensin II analogue is minimally affected by the binding of spike protein. These findings may have implications for a better understanding of COVID-19 pathogenesis.

Keywords: ACE2; COVID-19; SARS-CoV-2; spike protein.

MeSH terms

  • Angiotensin-Converting Enzyme 2 / metabolism*
  • Catalysis
  • Humans
  • Protein Binding
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / metabolism*
  • Spike Glycoprotein, Coronavirus / metabolism*
  • Substrate Specificity

Substances

  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2