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

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1, 211111, 3111, 3111LegendAngiotensin 1-9Spike vaccineTissue productionAnti-atrophyAngiotensin 1MAS1AT1RAGTRENAngiotensin 2ACEAngiotensin 1-7Anti-fibrosisAnti-InflammationAnti-oxidantVasodilationPro-atrophyPro-fibrosisPro-InflammationPro-oxidantVasoconstrictionSARS-CoV-2TMPRSS21, 3ACE2 surface receptor blockerSoluble ACE2 TMPRSS2 inhibitorSARS-CoV-2 and angiotensin-converting enzyme 2 (ACE2) receptor: Molecular mechanisms and potential therapeutic targetSARS-CoV-2 spike proteinViral membraneInhibitionDownregulationHost proteases for S proteinprimingACE2Entry for viral replicationARBs surface receptor blockerInhibitorsSARS-CoV-2SARS-CoV-2S1S2Activation of angiotensin pathwayConverting enzymeSARS-CoV-2Soluble ACE2Tissue injuryAccumulation of angiotensin


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.


Literature curation of biological processes involved in the COVID-19 disease after SARS-Cov-2 infection and molecular mechanism and potential therapeutic target

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  1. Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS; ''Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target.''; Intensive Care Med, 2020 PubMed Europe PMC Scholia
  2. Muthiah Vaduganathan, M.D., M.P.H., Orly Vardeny, Pharm.D., Thomas Michel, M.D., Ph.D., John J.V. McMurray, M.D., Marc A. Pfeffer, M.D., Ph.D., and Scott D. Solomon, M.D.; ''Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19''; DOI: 10.1056/NEJMsr2005760, 2020 PubMed Europe PMC Scholia
  3. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Müller MA, Drosten C, Pöhlmann S; ''SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor.''; Cell, 2020 PubMed Europe PMC Scholia


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120620view00:29, 19 December 2021EweitzTighten graphics, refine case
120511view12:25, 10 December 2021EweitzModified title
118877view12:04, 3 June 2021EweitzOntology Term : 'COVID-19' added !
116626view11:09, 9 May 2021EweitzModified title
115854view15:42, 18 March 2021Mkutmonmoved references to interactions
115851view15:30, 18 March 2021Mkutmonclean up description
115850view15:25, 18 March 2021Mkutmonannotations
115846view15:20, 18 March 2021Mkutmonannotated datanodes
115281view12:57, 9 February 2021EgonwAdded three missing DataNode types
114101view18:28, 22 December 2020EgonwConverted more Labels to DataNodes.
113633view12:05, 8 November 2020EgonwConverted three interacting Labels to DataNodes.
111819view04:42, 9 September 2020KhanspersModified description
111818view04:39, 9 September 2020Khanspersremoved receptor symbol, updated enzymatic reactions, cleanup
111621view07:55, 30 August 2020EgonwModified title
111614view20:41, 29 August 2020EgonwModified title
110813view22:38, 9 June 2020Mkutmonfixed publication references
110812view22:32, 9 June 2020Mkutmonfixed unconnected line
110575view05:21, 19 May 2020EgonwAdded missing @Type annotation
110550view10:14, 18 May 2020FehrhartModified title
110549view10:13, 18 May 2020FehrhartOntology Term : 'severe acute respiratory syndrome' added !
110548view10:13, 18 May 2020FehrhartOntology Term : 'angiotensin signaling pathway' added !
110547view10:12, 18 May 2020Fehrhartchanged interactions to graphical lines, added IDs for angiotensins
110047view08:24, 15 April 2020PennyReverted to version '16:56, 6 April 2020' by Penny
110046view08:02, 15 April 2020PennyUpdated connection between ACE2 and AGT
109915view16:56, 6 April 2020KhanspersOntology Term : 'viral infectious disease' added !
109885view16:50, 3 April 2020Rex D A BInteractions
109883view14:48, 3 April 2020Rex D A BModified description
109882view14:46, 3 April 2020Rex D A BModified description
109881view14:45, 3 April 2020Rex D A BNew pathway

External references


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NameTypeDatabase referenceComment
ACEProtein1636 (Entrez Gene)
ACE2 surface receptor blockerMetaboliteCHEBI:90710 (ChEBI)
ACE2GeneProduct59272 (Entrez Gene)
AGTGeneProduct183 (Entrez Gene)
ARBs surface receptor blockerMetaboliteCHEBI:90710 (ChEBI)
AT1RGeneProduct185 (Entrez Gene)
Angiotensin 1-7MetaboliteCHEBI:55438 (ChEBI)
Angiotensin 1-9MetaboliteCHEBI:80128 (ChEBI)
Angiotensin 1Metabolite2718 (ChEBI)
Angiotensin 2Metabolite2719 (ChEBI)
MAS1GeneProduct4142 (Entrez Gene)
RENGeneProduct5972 (Entrez Gene)
Soluble ACE2 Protein59272 (Entrez Gene)
Soluble ACE2GeneProduct59272 (Entrez Gene)
TMPRSS2 inhibitorMetaboliteCHEBI:35222 (ChEBI)
TMPRSS2GeneProductENSG00000184012 (Ensembl)

Annotated Interactions

No annotated interactions
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