Downregulation of ACE2 by SARS-CoV-2 spike protein (WP4799)

Homo sapiens

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.


Amber Koning , Friederike Ehrhart , Alex Pico , Egon Willighagen , Nhung Pham , and Eric Weitz


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Homo sapiens




Disease Ontology

COVID-19 viral infectious disease respiratory failure

Pathway Ontology

disease pathway


Label Type Compact URI Comment
Angiotensin II Metabolite chebi:2719
AT1R Protein uniprot:P30556
SARS-CoV-2 spike Protein uniprot:P0DTC2
ACE2 Protein uniprot:Q9BYF1
ACE Protein uniprot:A0A0A0MSN4
AT2R Protein uniprot:P50052


  1. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, et al. Nat Med. 2005 Aug;11(8):875–9. PubMed Europe PMC Scholia