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

From WikiPathways

Revision as of 11:24, 2 August 2020 by Egonw (Talk | contribs)
Jump to: navigation, search
2020surfaceglycoprotein S13211624142241092455, 17, 19Protein ExpressionVirionHuman cellType I InterferonInduction andSignalingtrimerNSP3-NSP4-NSP6complexTLR7complexpolymerasecomplexTMPRSS4Hijack ofUbiquitinationSLC6A19Integrative stressresponseFURIN40Snsp1CTSLPathogenesisActivation of NLRP3Inflammasome213624S2 subunitSARS-CoV-2proteinsorf1a15TMPRSS25, 18orf1abACE2dimerORF3aORF6ORF7aORF8nucleocapsidprotein4membraneglycoprotein4envelopeprotein4surfaceglycoprotein4, 7SARS-CoV-2RNAorf1ORF3aORF6ORF7aORF8ORF10nucleocapsidphosphoproteinmembraneglycoproteinenvelopeproteinsurfaceglycoproteinsurfaceglycoprotein Ssurfaceglycoprotein S4, 7membraneglycoprotein M4orf1abnsp2PL2-PRO3CL-PRO22nsp4nsp7nsp8nsp9nsp10nsp128, 11, 22nsp13ExoN8nsp15nsp16nsp6nsp5SARS-CoV-2RNAnucleocapsidprotein N4envelopeprotein E4ORF10nsp9nsp9orf1ORF7bORF7bnsp16nsp10surfaceglycoprotein Ssurfaceglycoprotein Ssurfaceglycoprotein SACE2recognition complexVirionPL2-PROnsp4nsp6surfaceglycoprotein Ssurfaceglycoprotein Ssurfaceglycoprotein SACE2recognition complexVirionORF3ansp9nsp10nsp1-40Scomplexnsp1ORF14S2 subunitnsp8NRP19EndocytosisVirionorf1nsp7nsp8nsp128, 11, 22orf1aborf1abcomplexType I InterferonInduction andSignaling12


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. 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.

Quality Tags

Ontology Terms



View all...
  1. 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
  2. Dömling A, Gao L; ''Chemistry and Biology of SARS-CoV-2.''; Chem, 2020 PubMed Europe PMC Scholia
  3. van der Made CI, Simons A, Schuurs-Hoeijmakers J, van den Heuvel G, Mantere T, Kersten S, van Deuren RC, Steehouwer M, van Reijmersdal SV, Jaeger M, Hofste T, Astuti G, Corominas Galbany J, van der Schoot V, van der Hoeven H, Hagmolen Of Ten Have W, Klijn E, van den Meer C, Fiddelaers J, de Mast Q, Bleeker-Rovers CP, Joosten LAB, Yntema HG, Gilissen C, Nelen M, van der Meer JWM, Brunner HG, Netea MG, van de Veerdonk FL, Hoischen A; ''Presence of Genetic Variants Among Young Men With Severe COVID-19'';, 2020
  4. 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
  5. Ogando NS, Zevenhoven-Dobbe JC, van der Meer Y, Bredenbeek PJ, Posthuma CC, Snijder EJ; ''The Enzymatic Activity of the nsp14 Exoribonuclease Is Critical for Replication of MERS-CoV and SARS-CoV-2.''; J Virol, 2020 PubMed Europe PMC Scholia
  6. 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'';, 2020
  7. Azad GK; ''Identification of novel mutations in themethyltransferase complex (Nsp10-Nsp16) of SARS-CoV-2.''; Biochem Biophys Rep, 2020 PubMed Europe PMC Scholia
  8. 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
  9. 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
  10. '''';,
  11. 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
  12. 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
  13. Ludovico Cantuti-Castelvetri, et al.; ''Neuropilin-1 facilitates SARS-CoV-2 cell entry and provides a possible pathway into the central nervous system'';, 2020
  14. 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
  15. van der Made CI, Simons A, Schuurs-Hoeijmakers J, van den Heuvel G, Mantere T, Kersten S, van Deuren RC, Steehouwer M, van Reijmersdal SV, Jaeger M, Hofste T, Astuti G, Corominas Galbany J, van der Schoot V, van der Hoeven H, Hagmolen Of Ten Have W, Klijn E, van den Meer C, Fiddelaers J, de Mast Q, Bleeker-Rovers CP, Joosten LAB, Yntema HG, Gilissen C, Nelen M, van der Meer JWM, Brunner HG, Netea MG, van de Veerdonk FL, Hoischen A; ''Presence of Genetic Variants Among Young Men With Severe COVID-19.''; JAMA, 2020 PubMed Europe PMC Scholia
  16. Clausen TM, Sandoval DR, Spliid CB, Pihl J, Perrett HR, Painter CD, Narayanan A, Majowicz SA, Kwong EM, McVicar RN, Thacker BE, Glass CA, Yang Z, Torres JL, Golden GJ, Bartels PL, Porell RN, Garretson AF, Laubach L, Feldman J, Yin X, Pu Y, Hauser BM, Caradonna TM, Kellman BP, Martino C, Gordts PLSM, Chanda SK, Schmidt AG, Godula K, Leibel SL, Jose J, Corbett KD, Ward AB, Carlin AF, Esko JD; ''SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2.''; Cell, 2020 PubMed Europe PMC Scholia
  17. ''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
  18. Wei C, Wan L, Yan Q, Wang X, Zhang J, Yang X, Zhang Y, Fan C, Li D, Deng Y, Sun J, Gong J, Wang Y, Li J, Yang H, Li H, Zhang Z, Wang R, Du P, Zong Y, Yin F, Zhang W, Wang N, Peng Y, Lin H, Feng J, Qin C, Chen W, Gao Q, Zhang R, Cao Y, Zhong H; ''HDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry.''; Nat Metab, 2020 PubMed Europe PMC Scholia
  19. 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
  20. Kim SY, Jin W, Sood A, Montgomery DW, Grant OC, Fuster MM, Fu L, Dordick JS, Woods RJ, Zhang F, Linhardt RJ; ''Characterization of heparin and severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) spike glycoprotein binding interactions.''; Antiviral Res, 2020 PubMed Europe PMC Scholia
  21. Edwards MJ, Becker KA, Gripp B, Hoffmann M, Keitsch S, Wilker B, Soddemann M, Gulbins A, Carpinteiro E, Patel SH, Wilson GC, Pöhlmann S, Walter S, Fassbender K, Ahmad SA, Carpinteiro A, Gulbins E; ''Sphingosine prevents binding of SARS-CoV-2 spike to its cellular receptor ACE2.''; J Biol Chem, 2020 PubMed Europe PMC Scholia
  22. 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
  23. 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
  24. 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
  25. Thoms M, Buschauer R, Ameismeier M, Koepke L, Denk T, Hirschenberger M, Kratzat H, Hayn M, Mackens-Kiani T, Cheng J, Straub JH, Stürzel CM, Fröhlich T, Berninghausen O, Becker T, Kirchhoff F, Sparrer KMJ, Beckmann R; ''Preprint: "Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2"''; 10.1101/2020.05.18.102467v1, 2020
  26. Eskier D, Suner A, Oktay Y, Karakülah G; ''Mutations of SARS-CoV-2 nsp14 exhibit strong association with increased genome-wide mutation load.''; PeerJ, 2020 PubMed Europe PMC Scholia
  27. Littler DR, Gully BS, Colson RN, Rossjohn J; ''Crystal Structure of the SARS-CoV-2 Non-structural Protein 9, Nsp9.''; iScience, 2020 PubMed Europe PMC Scholia
  28. 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
  29. 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
  30. 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
  31. 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
  32. Pique-Regi R, Romero R, Tarca AL, Luca F, Xu Y, Alazizi A, Leng Y, Hsu CD, Gomez-Lopez N; ''Does the human placenta express the canonical cell entry mediators for SARS-CoV-2?''; Elife, 2020 PubMed Europe PMC Scholia
  33. Wang S, Li W, Hui H, Tiwari SK, Zhang Q, Croker BA, Rawlings S, Smith D, Carlin AF, Rana TM; ''Cholesterol 25-Hydroxylase inhibits SARS-CoV-2 and other coronaviruses by depleting membrane cholesterol.''; EMBO J, 2020 PubMed Europe PMC Scholia


View all...
114429view19:16, 10 January 2021EgonwCholesterol depletion results in inhibition of membrane fusion.
114428view18:14, 10 January 2021EgonwAdded an alternative uptake mechanism.
114246view13:22, 29 December 2020EgonwTwo more articles
114234view06:23, 28 December 2020EgonwAdded a reported role of nsp14
113854view20:14, 1 December 2020EgonwAdded a role suggested for sphingosine.
113819view10:11, 28 November 2020EgonwAdded citation for nsp9 crystal structure and added heparan sulfate binding
113702view08:59, 17 November 2020Fehrhartsmall graphical updates
111980view19:27, 13 September 2020EgonwMore literature references linked to interactions.
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:
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.

External references


View all...
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)
NRP1ProteinO14786 (Uniprot-TrEMBL)
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
SARS-CoV-2 RNARnaQ82069695 (Wikidata)
SARS-CoV-2 proteinsProteinQ82069695 (Wikidata)
SLC6A19GeneProductENSG00000174358 (Ensembl)
TLR7ProteinQ9NYK1 (Uniprot-TrEMBL)
TMPRSS2ProteinO15393 (Uniprot-TrEMBL)
TMPRSS4ProteinQ9NRS4 (Uniprot-TrEMBL)
Type I Interferon

Induction and

PathwayWP4868 (WikiPathways)
complexComplexCPX-5685 (Complex Portal)
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)
polymerase complexComplexCPX-5742 (Complex Portal)
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

Personal tools