The role of angiotensin-converting enzyme 2 (ACE2) in SARS-CoV-2 (severe acute respiratory syndrome Coronavirus-2) infection process

Abstract

SARS-CoV-2 can cause severe acute respiratory illness and multi-organ injury. Angiotensin-converting enzyme 2 (ACE2) is an important enzyme of the renin-angiotensin system (RAS), which is the main receptor for entry of SARS-CoV-2 into host cells. Both cell surface ACE2 and soluble ACE2 (sACE2) can interact with the receptor binding domain (RBD) in SARS-CoV-2 S protein. After binding to cell surface ACE2, SARS-CoV-2 enters host cells by direct fusion of the viral with host cell membranes with the support of host’s TMPRSS2 (transmembrane serine protease 2) and furin. In contrast, sACE2-bound SARS-CoV-2 enters host cells through AT1 (Angiotensin type 1 receptor) and AVPR1B (arginine vasopressin receptor 1B). The entery process strongly down regulates membrane-bound ACE2, promoting an activation of the canonical pathway of RAS (ACE-Ang II-AT1 receptor axis). Consequently, this promotes an intense activity of NF-kB (nuclear factor kappa B), which in turn increases the transcription of IL-6, and triggers the cytokine storm. Moreover, the decreasing of ACE2 function in lung leed to the activation of DABK/BKB1R axis signaling, contributing to the pathogenesis of acute lung inflammation. This review summarizes information about the role of ACE2 in SARS-CoV-2 infection and Covid-19, also the research directions for prevention and treatment of Covid-19 which based on ACE2.