Downregulation of ACE2 by SARS-CoV-2 spike protein

Schematic diagram of the renin-angiotensin system in acute lung failure and proposed SARS-CoV action. The renin-angiotensin system has a crucial role in severe acute lung injury and the SARS-CoV receptor ACE2 has a protective role in acute lung failure. Because ACE2 is a crucial SARS-CoV receptor, SARS-CoV Spike protein binding to ACE2 downmodulates ACE2 expression, and loss of ACE2 expression results in severe acute respiratory failure. The AT1R is the crucial receptor that mediates AngII-induced vascular permeability and severe acute lung injury. SARS-CoV Spike–mediated lung failure can be rescued by inhibition of AT1R. This research was done in in vivo mice cells.

急性肺衰竭中肾素-血管紧张素系统的示意图及SARS-CoV作用机制之探讨。肾素-血管紧张素系统在严重急性肺损伤中扮演关键角色，而SARS-CoV受体ACE2在急性肺衰竭中具有保护性作用。鉴于ACE2是SARS-CoV的关键受体，SARS-CoV刺突蛋白与ACE2的结合会下调ACE2的表达，ACE2表达量的减少导致严重的急性呼吸衰竭。AT1R是介导AngII诱导的血管通透性和严重急性肺损伤的关键受体。通过抑制AT1R，可以挽救由SARS-CoV刺突蛋白介导的肺衰竭。本研究在体内小鼠细胞中进行。