SARS-CoV-2 and ACE2 receptor: molecular mechanisms (WP4883)

Homo sapiens

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For initial entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into cells, the large viral Spike (S) protein needs to be primed by host proteases. For SARS-CoV-2 that is the serine protease TMPRSS2. After binding to its functional receptor, angiotensin-converting enzyme 2 (ACE2), the virus undergoes endocytosis. After endocytosis of the viral complex, surface ACE2 is further down-regulated, resulting in unopposed angiotensin 2 accumulation. Local activation of the angiotensin pathway system may mediate lung injury responses to viral insults. ACE denotes angiotensin-converting enzyme and ARB angiotensin-receptor blocker.

Authors

Rex D A B , Kristina Hanspers , Penny Nymark , Friederike Ehrhart , Egon Willighagen , Martina Summer-Kutmon , and Eric Weitz

Activity

last edited

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Organisms

Homo sapiens

Communities

COVID-19

Annotations

Pathway Ontology

angiotensin signaling pathway

Disease Ontology

COVID-19 severe acute respiratory syndrome viral infectious disease

Participants
Query Drugst.One

Label Type Compact URI Comment
Angiotensin 1-9 Metabolite chebi:80128
Angiotensin 2 Metabolite chebi:2719
Angiotensin 1 Metabolite chebi:2718
Angiotensin 1-7 Metabolite chebi:55438
ACE2 surface receptor blocker Metabolite chebi:90710
TMPRSS2 inhibitor Metabolite chebi:35222
ARBs surface receptor blocker Metabolite chebi:90710
REN GeneProduct ncbigene:5972
MAS1 GeneProduct ncbigene:4142
AGT GeneProduct ncbigene:183
AT1R GeneProduct ncbigene:185
TMPRSS2 GeneProduct ensembl:ENSG00000184012
ACE2 GeneProduct ncbigene:59272
Soluble ACE2 GeneProduct ncbigene:59272
ACE Protein ncbigene:1636
Soluble ACE2 Protein ncbigene:59272

References

  1. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Intensive Care Med. 2020 Apr;46(4):586–90. PubMed Europe PMC Scholia
  2. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. Cell. 2020 Apr 16;181(2):271-280.e8. PubMed Europe PMC Scholia
  3. Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Covid-19. Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. N Engl J Med. 2020 Apr 23;382(17):1653–9. PubMed Europe PMC Scholia