SARS-CoV-2 and COVID-19 Pathway (Homo sapiens)

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99surfaceglycoprotein S5413412412157, 11, 15Protein ExpressionVirionHuman cellcomplexPathogenesistrimerHijack ofUbiquitinationType I InterferonInduction andSignalingSLC6A19Integrative stressresponseTMPRSS4FURIN40SNSP3-NSP4-NSP6complexActivation of NLRP3Inflammasomensp1CTSL412314S2 subunitSARS-CoV-2proteinsorf1a8TMPRSS215orf1abACE2dimerORF3aORF6ORF7aORF8nucleocapsidprotein1membraneglycoprotein1envelopeprotein1surfaceglycoprotein1, 2SARS-CoV-2RNAorf1ORF3aORF6ORF7aORF8ORF10nucleocapsidphosphoproteinmembraneglycoproteinenvelopeproteinsurfaceglycoproteinsurfaceglycoprotein Ssurfaceglycoprotein S1, 2membraneglycoprotein M1orf1abnsp2PL2-PRO3CL-PROnsp4nsp7nsp8nsp9nsp10nsp126, 10nsp13ExoN10nsp15nsp16nsp6nsp5SARS-CoV-2RNAnucleocapsidprotein N1envelopeprotein E1ORF10nsp9nsp9orf1ORF7bORF7bnsp16nsp10surfaceglycoprotein Ssurfaceglycoprotein Ssurfaceglycoprotein SACE2recognition complexVirionPL2-PROnsp4nsp6surfaceglycoprotein Ssurfaceglycoprotein Ssurfaceglycoprotein SACE2recognition complexVirionORF3ansp9nsp10nsp1-40Scomplexnsp1ORF14TMPRSS2S2 subunit12S2' subunit


Collaborative project for curation biological processes involved in the COVID-19 disease after SARS-Cov-2 infection. It focuses on experimental evidence and plays with improved annotation of complexes and with the Evidence and Conclusion Ontology. The complexes link to EBI's Complex Portal, resulting from a collaboration with that database at the recent online ELIXIR biohackathon.

Editing this pathway is (at this moment) coordinated via the #sarscov2 channel.

The large viral Spike protein (S or surface glycoprotein) forms trimers. It interacts with the host's ACE2 receptor to establish binding (Hoffmann et al 2020). There are suggestions for more than one cell entry mechanism, with the evidence for ACE2/TMPRSS2 entry being most clear now. Lack of expression of TMPRSS2 may explain age differences in COVID19 severity. In this mechanism, to enter the virus needs to be primed by the host protease TMPRSS2 that splits the Spike protein into 2 peptides S1 and S2. S1 contains the ACE2 receptor binding site, S2 binds to the host cell membrane which leads to membrane fusion, the start of the uptake process. The ACE2 receptor interaction was also suggested as the start of specific lung-damaging effects.

Other human genes that may be involved in alternative cell uptake mechanisms include CTSL and SLC6A19.

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  1. Kandeel M, Ibrahim AA, Fayez M, Al-Nazawi M; ''From SARS and MERS CoVs to SARS-CoV-2: moving toward more biased codon usage in viral structural and non-structural genes.''; J Med Virol, 2020 PubMed Europe PMC Scholia
  2. Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D; ''Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein.''; Cell, 2020 PubMed Europe PMC Scholia
  3. ''Simultaneous Treatment of COVID-19 With Serine Protease Inhibitor Camostat and/or Cathepsin L Inhibitor'';, 2020
  4. ''Preprint: "Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2"''; 10.1101/2020.05.18.102467v1, 2020
  5. Tan K, Kim Y, Jedrzejczak R, Maltseva N, Endres M, Michalska K, Joachimiak A, Center for Structural Genomics of Infectious Diseases (CSGID); ''The crystal structure of Nsp9 replicase protein of COVID-19'';, 2020
  6. Pachetti M, Marini B, Benedetti F, Giudici F, Mauro E, Storici P, Masciovecchio C, Angeletti S, Ciccozzi M, Gallo RC, Zella D, Ippodrino R; ''Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant.''; J Transl Med, 2020 PubMed Europe PMC Scholia
  7. Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q; ''Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2.''; Science, 2020 PubMed Europe PMC Scholia
  8. Li C, Yang Y, Ren L; ''Genetic evolution analysis of 2019 novel coronavirus and coronavirus from other species.''; Infect Genet Evol, 2020 PubMed Europe PMC Scholia
  9. Sigrist CJ, Bridge A, Le Mercier P; ''A potential role for integrins in host cell entry by SARS-CoV-2.''; Antiviral Res, 2020 PubMed Europe PMC Scholia
  10. Shannon A, Le NT, Selisko B, Eydoux C, Alvarez K, Guillemot JC, Decroly E, Peersen O, Ferron F, Canard B; ''Remdesivir and SARS-CoV-2: Structural requirements at both nsp12 RdRp and nsp14 Exonuclease active-sites.''; Antiviral Res, 2020 PubMed Europe PMC Scholia
  11. 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
  12. ''Preprint: TMPRSS2 and furin are both essential for proteolytic activation and spread of SARS-1 CoV-2 in human airway epithelial cells and provide promising drug targets''; 10.1101/2020.04.15.042085v1, 2020
  13. Angelini MM, Akhlaghpour M, Neuman BW, Buchmeier MJ; ''Severe acute respiratory syndrome coronavirus nonstructural proteins 3, 4, and 6 induce double-membrane vesicles.''; mBio, 2013 PubMed Europe PMC Scholia
  14. Zang R, Gomez Castro MF, McCune BT, Zeng Q, Rothlauf PW, Sonnek NM, Liu Z, Brulois KF, Wang X, Greenberg HB, Diamond MS, Ciorba MA, Whelan SPJ, Ding S; ''TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes.''; Sci Immunol, 2020 PubMed Europe PMC Scholia
  15. 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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110668view18:35, 27 May 2020EgonwMade a few pathway nodes have a shape
110650view05:27, 25 May 2020EgonwAdded the missing protein identifier
110619view16:04, 21 May 2020EgonwOkay, it's getting complex :/
110618view15:42, 21 May 2020EgonwAdded two more recent papers (HT Chem2W)
110617view15:05, 21 May 2020EgonwAdded a new protein reported by UniProt.
110616view10:32, 21 May 2020EgonwAdded the Wikidata identifier for nsp1
110615view10:13, 21 May 2020EgonwLinked the preprint also to the inhibition interaction.
110614view10:12, 21 May 2020EgonwAdded the ECO code
110613view09:41, 21 May 2020EgonwFirst bit of conclusions captured.
110612view08:55, 21 May 2020EgonwAdded a preprint about nsp1 ribosome binding.
110577view08:11, 19 May 2020EveloModified description
110576view07:44, 19 May 2020EveloModified description
110551view10:17, 18 May 2020Fehrhartfixed the one and only unconnected line
110543view09:50, 18 May 2020FehrhartOntology Term : 'severe acute respiratory syndrome' added !
110540view19:13, 17 May 2020EgonwAdded another ref for nsp12 (about variations)
110539view18:18, 17 May 2020EgonwAdded a literature reference for nsp12 and nsp14
110538view18:11, 17 May 2020EgonwAdded more nsp identifiers
110531view12:38, 17 May 2020EgonwOne more tweak
110530view12:37, 17 May 2020EgonwMade the pathway nodes a bit larger, hoping the label does not fully show up
110528view12:08, 17 May 2020EgonwUpdated the protein colors
110527view12:05, 17 May 2020EgonwMarked the virus RNA as @Type=Rna
110526view12:01, 17 May 2020EgonwAdded in related WikiPathways
110519view20:06, 16 May 2020EgonwModified description
110518view20:00, 16 May 2020EgonwAdded an experimental complex that hypothesizes involvement of SLC6A19. And added initial ECO annotation.
110482view19:04, 13 May 2020EgonwCTSL is now UniProt/Protein too.
110481view18:44, 13 May 2020EgonwColored the protein N.
110480view18:41, 13 May 2020EgonwAlso updated TMRPSS2
110479view18:39, 13 May 2020EgonwChanged ACE2 to Protein
110475view16:54, 13 May 2020EgonwAdded a new gene mentioned.
110308view16:05, 3 May 2020EgonwAdded missing @Type annotation
110192view17:12, 23 April 2020EgonwFixed type of the human proteins.
110116view19:37, 17 April 2020EgonwAdded a few more complexes.
110115view19:18, 17 April 2020EgonwDrew the spike protein trimer and added the Complex Portal identifier.
110061view06:57, 16 April 2020EgonwAdded ORF7b
109992view13:45, 9 April 2020EgonwColored more virus proteins.
109991view13:40, 9 April 2020Egonw
109990view13:37, 9 April 2020EgonwMoved the protein splitting into the human cell (where it happens) and added a dimer complex.
109968view18:15, 8 April 2020AlexanderPicoupdated sars nodes per #covidpathways guidelines
109954view18:45, 7 April 2020EgonwAdded an identifier
109857view13:48, 2 April 2020MaintBotStyled the virus nodes.
109839view01:45, 2 April 2020AlexanderPicoupdated Orf10 protein xref
109838view01:31, 2 April 2020AlexanderPicoupdated Wikidata entries and xrefs for ORF6, 7a and 8 proteins
109837view01:00, 2 April 2020AlexanderPicoalt protein xref for orf8
109836view00:58, 2 April 2020AlexanderPicofixed nsp8 to ORF8
109835view00:56, 2 April 2020AlexanderPicochanged ns6 to ORF6
109829view22:04, 1 April 2020AlexanderPicoupdated Orf10 xref
109777view21:17, 31 March 2020EveloAdded ORF10 protein product and moves S2 inside host membrane where it leads to fusion
109776view20:46, 31 March 2020EveloModified description
109773view13:47, 31 March 2020EveloS2 subunit connected to host cell (prepares for fusion). Transcription interactions added
109735view06:27, 30 March 2020EgonwAdded another Wikidata identifier

External references


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NameTypeDatabase referenceComment
3CL-PROProteinQ87917582 (Wikidata)
40SComplexCPX-5223 (Complex Portal)
ACE2ProteinQ9BYF1 (Uniprot-TrEMBL)
Activation of


PathwayWP4876 (WikiPathways)
CTSLProteinP07711 (Uniprot-TrEMBL)
ExoNProteinQ94648393 (Wikidata) nsp14
FURINProteinP09958 (Uniprot-TrEMBL)
Hijack of UbiquitinationPathwayWP4860 (WikiPathways)
Integrative stress responsePathwayWP4861 (WikiPathways)
NSP3-NSP4-NSP6 complexComplexCPX-5691 (Complex Portal)
ORF10GeneProduct43740576 (Entrez Gene)
ORF10ProteinQ89227548 (Wikidata)
ORF14ProteinP0DTD3 (Uniprot-TrEMBL)
ORF3aGeneProduct43740569 (Entrez Gene)
ORF3aProteinP0DTC3 (Uniprot-TrEMBL)
ORF6GeneProduct43740572 (Entrez Gene)
ORF6ProteinQ89226299 (Wikidata)
ORF7aGeneProduct43740573 (Entrez Gene)
ORF7aProteinQ88658500 (Wikidata)
ORF7bGeneProduct43740574 (Entrez Gene)
ORF7bProteinQ88089438 (Wikidata)
ORF8GeneProduct43740577 (Entrez Gene)
ORF8ProteinQ89225654 (Wikidata)
PL2-PROProteinQ87917581 (Wikidata) nsp3
PathogenesisPathwayWP4884 (WikiPathways)
S2 subunitProtein
S2' subunitProtein
SARS-CoV-2 RNARnaQ82069695 (Wikidata)
SARS-CoV-2 proteinsProteinQ82069695 (Wikidata)
SLC6A19GeneProductENSG00000174358 (Ensembl)
TMPRSS2ProteinO15393 (Uniprot-TrEMBL)
TMPRSS4ProteinQ9NRS4 (Uniprot-TrEMBL)
Type I Interferon

Induction and

PathwayWP4868 (WikiPathways)
complexComplexCPX-5688 (Complex Portal)
dimerComplexCPX-5687 (Complex Portal)
envelope protein EProteinP0DTC4 (Uniprot-TrEMBL)
envelope proteinGeneProduct43740570 (Entrez Gene)
envelope proteinProteinP0DTC4 (Uniprot-TrEMBL)
membrane glycoprotein MProteinP0DTC5 (Uniprot-TrEMBL)
membrane glycoproteinGeneProduct43740571 (Entrez Gene)
membrane glycoproteinProteinP0DTC5 (Uniprot-TrEMBL)


nsp10ProteinQ87917572 (Wikidata) nsp10
nsp12ProteinQ94647436 (Wikidata) RdRp
nsp13ProteinQ94648377 (Wikidata) Helicase
nsp15ProteinQ87917579 (Wikidata) NendoU
nsp16ProteinQ87917579 (Wikidata) 2'-O-methyltransferase
nsp1ProteinQ90038952 (Wikidata) Host translation inhibitor nsp1
nsp2ProteinQ89006922 (Wikidata)
nsp4ProteinQ90038956 (Wikidata)
nsp5ProteinQ87917582 (Wikidata)
nsp6ProteinQ88656943 (Wikidata)
nsp7ProteinQ90038963 (Wikidata)
nsp8ProteinQ88659350 (Wikidata)
nsp9ProteinQ89686805 (Wikidata)
nucleocapsid phosphoproteinGeneProduct43740575 (Entrez Gene)
nucleocapsid protein NProteinP0DTC9 (Uniprot-TrEMBL)
nucleocapsid proteinProteinP0DTC9 (Uniprot-TrEMBL)
orf1GeneProduct43740578 (Entrez Gene)
orf1aProteinP0DTC1 (Uniprot-TrEMBL)
orf1abProteinP0DTD1 (Uniprot-TrEMBL)
recognition complexComplexCPX-5683 (Complex Portal)
recognition complexComplexCPX-5684 (Complex Portal)
surface glycoprotein SProteinP0DTC2 (Uniprot-TrEMBL)
surface glycoproteinGeneProduct43740568 (Entrez Gene)
surface glycoproteinProteinP0DTC2 (Uniprot-TrEMBL)
trimerComplexCPX-5682 (Complex Portal)

Annotated Interactions

No annotated interactions

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