SARS-CoV-2 spike protein binding selectively accelerates substrate-specific catalytic activity of ACE2.
J Biochem
; 170(2): 299-306, 2021 Oct 11.
Article
en En
| MEDLINE
| ID: mdl-33774672
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Glicoproteína de la Espiga del Coronavirus
/
Enzima Convertidora de Angiotensina 2
/
SARS-CoV-2
Límite:
Humans
Idioma:
En
Revista:
J Biochem
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos