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

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1515surfaceglycoprotein S1108164101041311-13Protein ExpressionVirionHuman cellNSP3-NSP4-NSP6complexActivation of NLRP3InflammasomecomplexTMPRSS4Integrative stressresponseSLC6A19trimerType I InterferonInduction andSignalingCTSLFURIN40SPathogenesisnsp1Hijack ofUbiquitination910414S2 subunitSARS-CoV-2proteinsorf1a7TMPRSS213orf1abACE2dimerORF3aORF6ORF7aORF8nucleocapsidprotein3membraneglycoprotein3envelopeprotein3surfaceglycoprotein3, 6SARS-CoV-2RNAorf1ORF3aORF6ORF7aORF8ORF10nucleocapsidphosphoproteinmembraneglycoproteinenvelopeproteinsurfaceglycoproteinsurfaceglycoprotein Ssurfaceglycoprotein S3, 6membraneglycoprotein M3orf1abnsp2PL2-PRO3CL-PROnsp4nsp7nsp8nsp9nsp10nsp122, 5nsp13ExoN2nsp15nsp16nsp6nsp5SARS-CoV-2RNAnucleocapsidprotein N3envelopeprotein E3ORF10nsp9nsp9orf1ORF7bORF7bnsp16nsp10surfaceglycoprotein Ssurfaceglycoprotein Ssurfaceglycoprotein SACE2recognition complexVirionPL2-PROnsp4nsp6surfaceglycoprotein Ssurfaceglycoprotein Ssurfaceglycoprotein SACE2recognition complexVirionORF3ansp9nsp10nsp1-40Scomplexnsp1ORF14TMPRSS2S2 subunit4S2' subunit


Description

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 wikipathways.slack.com #sarscov2 channel. Additionally, please feel free to add suggestions to the discussion page (see the tab at the top of this page).

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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Ontology Terms

 

Bibliography

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  2. Shang J, Wan Y, Luo C, Ye G, Geng Q, Auerbach A, Li F; ''Cell entry mechanisms of SARS-CoV-2.''; Proc Natl Acad Sci U S A, 2020 PubMed Europe PMC Scholia
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  4. ''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
  5. 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
  6. 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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  10. Hillen HS, Kokic G, Farnung L, Dienemann C, Tegunov D, Cramer P; ''Structure of replicating SARS-CoV-2 polymerase.''; Nature, 2020 PubMed Europe PMC Scholia
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  17. 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
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  19. 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
  20. Bittmann S, Weissenstein A, Villalon G, Moschuring-Alieva E, Luchter E; ''Simultaneous Treatment of COVID-19 With Serine Protease Inhibitor Camostat and/or Cathepsin L Inhibitor''; https://doi.org/10.14740/jocmr4161, 2020
  21. ''''; https://www.youtube.com/watch?v=e2Qi-hAXdJo,
  22. 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
  23. Ludovico Cantuti-Castelvetri, et al.; ''Neuropilin-1 facilitates SARS-CoV-2 cell entry and provides a possible pathway into the central nervous system''; https://doi.org/10.1101/2020.06.07.137802, 2020
  24. Rosas-Lemus M, Minasov G, Shuvalova L, Inniss NL, Kiryukhina O, Wiersum G, Kim Y, Jedrzejczak R, Maltseva NI, Endres M, Jaroszewski L, Godzik A, Joachimiak A, Satchell KJF; ''The crystal structure of nsp10-nsp16 heterodimer from SARS-CoV-2 in complex with S-adenosylmethionine.''; bioRxiv, 2020 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
111364view05:28, 3 August 2020EgonwConverted two interacting Label's to DataNode's.
111358view11:24, 2 August 2020EgonwAnother preprint is published now.
111357view11:18, 2 August 2020EgonwReplaced a DOI by the PubMed ID.
111348view04:56, 30 July 2020EgonwCompleted the TLR7 route, now with PubMed ID.
111317view09:38, 28 July 2020EgonwAdded new recent insight
111242view09:19, 27 July 2020EgonwAdded another reference.
111228view16:08, 26 July 2020EgonwRemoved another bit of info backed by the removed preprint.
111227view16:02, 26 July 2020EgonwRemoved a preprint marked for image duplication: https://pubpeer.com/publications/E7FD45D01851101DF958911F6F0F45
111226view15:59, 26 July 2020EgonwAdded another complex, and a nice YouTube video.
110895view09:40, 18 June 2020EgonwAdded another article about the role of FURIN
110894view06:59, 18 June 2020EgonwRestructured the map.
110893view06:49, 18 June 2020EgonwAdded NRP1
110890view20:54, 17 June 2020EgonwAdded the polymerase cmoplex.
110889view20:06, 17 June 2020EgonwA bit more literature
110886view17:44, 17 June 2020EgonwAdded another reference
110832view13:05, 11 June 2020Egonw
110811view22:26, 9 June 2020Mkutmonfix unconnected line
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.

External references

DataNodes

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

NLRP3

Inflammasome
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

Signaling
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)
nsp1-40S

complex

Complex
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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