Type I interferon induction and signaling during SARS-CoV-2 infection (Homo sapiens)

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3ISREINF-IInnate ImmunityGRL0617NucleusIkkeIRF3TRAF6IKKaMYD88IKKbTRAF3NFKBTBK1JAK1TREML4TLR7NEMOIkBaOAS1PKRPLpro (nsp3)1, 2AP-1NFkBMAP3K7MAPK8MAPK14JUNFOSIFNAR1IFNAR2TYK2STAT1STAT2IRF9INF-IINF-IISREISGsOAS2OAS3


Description

Type I interferon induction and signaling during SARS-COV-2 infection. Includes specific SARS-CoV-2 proteins (red ovals) and relevant drugs (blue rounded rectangles). Based on Figure 8 from Fung, et al. 2019. Inhibition of SARS-CoV-2 PLpro by GRL0617 is modeled based on Ratia, et al. 2008 and 100% sequence identity between SARS-CoV and SARS-CoV-2 across all 13 residues of PLpro involved in binding GRL0617 (82.9% identity across 316 amino acids).

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Bibliography

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  1. Ratia K, Pegan S, Takayama J, Sleeman K, Coughlin M, Baliji S, Chaudhuri R, Fu W, Prabhakar BS, Johnson ME, Baker SC, Ghosh AK, Mesecar AD; ''A noncovalent class of papain-like protease/deubiquitinase inhibitors blocks SARS virus replication.''; Proc Natl Acad Sci U S A, 2008 PubMed Europe PMC Scholia
  2. Edelmann MJ, Nicholson B, Kessler BM; ''Pharmacological targets in the ubiquitin system offer new ways of treating cancer, neurodegenerative disorders and infectious diseases.''; Expert Rev Mol Med, 2011 PubMed Europe PMC Scholia
  3. Ramirez-Ortiz ZG, Prasad A, Griffith JW, Pendergraft WF 3rd, Cowley GS, Root DE, Tai M, Luster AD, El Khoury J, Hacohen N, Means TK; ''The receptor TREML4 amplifies TLR7-mediated signaling during antiviral responses and autoimmunity.''; Nat Immunol, 2015 PubMed Europe PMC Scholia
  4. Aghai ZH, Kode A, Saslow JG, Nakhla T, Farhath S, Stahl GE, Eydelman R, Strande L, Leone P, Rahman I; ''Azithromycin suppresses activation of nuclear factor-kappa B and synthesis of pro-inflammatory cytokines in tracheal aspirate cells from premature infants.''; Pediatr Res, 2007 PubMed Europe PMC Scholia
  5. Baines KJ, Wright TK, Gibson PG, Powell H, Hansbro PM, Simpson JL; ''Azithromycin treatment modifies airway and blood gene expression networks in neutrophilic COPD.''; ERJ Open Res, 2018 PubMed Europe PMC Scholia
  6. Yamauchi K, Shibata Y, Kimura T, Abe S, Inoue S, Osaka D, Sato M, Igarashi A, Kubota I; ''Azithromycin suppresses interleukin-12p40 expression in lipopolysaccharideand interferon-gamma stimulated macrophages.''; Int J Biol Sci, 2009 PubMed Europe PMC Scholia
  7. Lei X, Dong X, Ma R, Wang W, Xiao X, Tian Z, Wang C, Wang Y, Li L, Ren L, Guo F, Zhao Z, Zhou Z, Xiang Z, Wang J; ''Activation and evasion of type I interferon responses by SARS-CoV-2.''; Nat Commun, 2020 PubMed Europe PMC Scholia
  8. Yamauchi K, Shibata Y, Kimura T, Abe S, Inoue S, Osaka D, Sato M, Igarashi A, Kubota I; ''Azithromycin suppresses interleukin-12p40 expression in lipopolysaccharide and interferon-gamma stimulated macrophages.''; Int J Biol Sci, 2009 PubMed Europe PMC Scholia
  9. Khanmohammadi S, Rezaei N; ''Role of Toll-like receptors in the pathogenesis of COVID-19.''; J Med Virol, 2021 PubMed Europe PMC Scholia
  10. Fung TS, Liu DX; ''Human Coronavirus: Host-Pathogen Interaction.''; Annu Rev Microbiol, 2019 PubMed Europe PMC Scholia
  11. Baines KJ, Wright TK, Gibson PG, Powell H, Hansbro PM, Simpson JL; ''Azithromycin treatment modifies airway and blood gene expression networks in neutrophilic COPD.''; ERJ Open Res, 2018 PubMed Europe PMC Scholia
  12. Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Dupont HT, Honoré S, Colson P, Chabrière E, La Scola B, Rolain JM, Brouqui P, Raoult D; ''Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial.''; Int J Antimicrob Agents, 2020 PubMed Europe PMC Scholia
  13. Sa Ribero M, Jouvenet N, Dreux M, Nisole S; ''''; , PubMed Europe PMC Scholia
  14. Carter-Timofte ME, Jørgensen SE, Freytag MR, Thomsen MM, Brinck Andersen NS, Al-Mousawi A, Hait AS, Mogensen TH; ''Deciphering the Role of Host Genetics in Susceptibility to Severe COVID-19.''; Front Immunol, 2020 PubMed Europe PMC Scholia
  15. Murgolo N, Therien AG, Howell B, Klein D, Koeplinger K, Lieberman LA, Adam GC, Flynn J, McKenna P, Swaminathan G, Hazuda DJ, Olsen DB; ''SARS-CoV-2 tropism, entry, replication, and propagation: Considerations for drug discovery and development.''; PLoS Pathog, 2021 PubMed Europe PMC Scholia
  16. Xia H, Cao Z, Xie X, Zhang X, Chen JY, Wang H, Menachery VD, Rajsbaum R, Shi PY; ''Evasion of Type I Interferon by SARS-CoV-2.''; Cell Rep, 2020 PubMed Europe PMC Scholia
  17. Xia H, Shi PY; ''Antagonism of Type I Interferon by Severe Acute Respiratory Syndrome Coronavirus 2.''; J Interferon Cytokine Res, 2020 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
135713view23:43, 29 October 2024EweitzTailor node width, standardize case
135712view23:23, 29 October 2024EweitzEconomize layout
125361view23:49, 6 February 2023AlexanderPicostarndardized colors, shapes, edges and labels; tidying up
124657view13:31, 18 November 2022NhungPupdate viral proteins shapes and remove legend
124431view12:46, 27 October 2022Mkutmonlower case SARS-CoV-2 protein names
120021view10:34, 15 October 2021FinterlyReverted to version '06:31, 6 June 2021' by Finterly
120006view04:41, 11 October 2021FinterlyChanged some of the "P" shapes to states.
118978view06:31, 6 June 2021EgonwTranslocation
118875view12:03, 3 June 2021EweitzOntology Term : 'COVID-19' added !
116599view19:13, 8 May 2021EweitzModified title
116223view09:42, 21 April 2021DeSlConnected "necessary stimulation was from TREMBL4 to the MYD88 recruitment by TLR7", and "inhibition STAT1 by nsp1"
116205view15:08, 19 April 2021AnnaNiCorrect node IDs, update references, confirm TLR3 and TLR7 pathways
116204view15:01, 19 April 2021DeSlUpdated database annotations for ORF6 and ORF3a from Swissprot to trembl
116155view10:24, 14 April 2021NhungPAdd TREML4 identifier and references
116153view08:53, 14 April 2021NhungPModified description
116152view08:41, 14 April 2021NhungPModified description
116151view08:23, 14 April 2021NhungPAdd axithromycin. Adjust layout
116143view13:16, 13 April 2021NhungPAdd SARS-CoV 2 proteins
116142view12:52, 13 April 2021NhungPAdjust layout. remove NFkB cytokine production pathway
116133view08:33, 13 April 2021NhungPAdd phosphorylated IRF3/7 dimer and IFN 1 alpha beta
116082view17:01, 9 April 2021NhungPAdd RIG-I, MDA5 and corresponding references. Working progress, don't remove
116079view10:28, 9 April 2021NhungPAdd tlr2,6,4, their cascades, and references. Work in progress. don't remove
116076view07:51, 9 April 2021NhungPUpdate literature
116061view14:25, 7 April 2021NhungPFix TLRs for 2 types of virus entry: diffusion and endocytosis. Working progress, don't remove
115857view15:52, 18 March 2021NhungPAdd references to interactions
115853view15:37, 18 March 2021NhungPUpdate nsp13-TBK1 interaction to inhibition. Corresponding literatures were also added to this inhibition
111110view09:08, 13 July 2020EgonwMake the linked pathway clickable (tho no identifier)
110206view10:53, 24 April 2020Fehrhartadded legend
110201view20:40, 23 April 2020EgonwTyped proteins as Type="Protein"
109974view18:19, 8 April 2020AlexanderPicoupdated sars nodes per #covidpathways guidelines
109832view23:31, 1 April 2020AlexanderPicoadded lit ref for clinical trial; removed stray datanode
109831view23:30, 1 April 2020AlexanderPicoModified description
109830view23:18, 1 April 2020AlexanderPicoAdded azithromycin
109785view00:54, 1 April 2020AlexanderPicoModified description
109763view02:05, 31 March 2020AlexanderPicoModified description
109762view21:15, 30 March 2020AlexanderPicoAdded nsp13 interaction and lit ref
109694view01:13, 29 March 2020AlexanderPicoModified description
109693view00:58, 29 March 2020AlexanderPicoModified title
109692view00:58, 29 March 2020AlexanderPicoUpdate to Ensembl IDs and HGNC labels
109691view00:49, 29 March 2020AlexanderPicoAdded RefSeq ID for PLpro(nsp3)
109690view00:35, 29 March 2020AlexanderPicoClarified NFKB
109689view00:14, 29 March 2020AlexanderPicoLayout tweaks
109688view00:08, 29 March 2020AlexanderPicoLayout tweaks; fixed TRAF6 path
109685view23:40, 28 March 2020AlexanderPicoAdded another ref for inhibition of PLpro by GRL0617
109684view23:37, 28 March 2020AlexanderPicoOntology Term : 'severe acute respiratory syndrome' added !
109683view23:37, 28 March 2020AlexanderPicoOntology Term : 'viral infectious disease' added !
109682view23:37, 28 March 2020AlexanderPicoOntology Term : 'signaling pathway' added !
109681view23:36, 28 March 2020AlexanderPicoOntology Term : 'type I interferon signaling pathway' added !
109680view22:56, 28 March 2020AlexanderPicoModified description
109679view22:50, 28 March 2020AlexanderPicoAdded lit refs

External references

DataNodes

View all...
NameTypeDatabase referenceComment
FOSGeneProductENSG00000170345 (Ensembl) NFKB not specified
GRL0617MetaboliteQ27097846 (Wikidata)
IFNAR1GeneProductENSG00000142166 (Ensembl)
IFNAR2GeneProductENSG00000159110 (Ensembl)
IKKaGeneProductO15111 (Uniprot-TrEMBL)
IKKbGeneProductO14920 (Uniprot-TrEMBL)
INF-IProtein
IRF3GeneProductENSG00000126456 (Ensembl)
IRF9GeneProductENSG00000213928 (Ensembl)
ISGsProtein
IkBaGeneProductP25963 (Uniprot-TrEMBL)
IkkeGeneProductENSG00000263528 (Ensembl)
Innate ImmunityPathway
JAK1GeneProductENSG00000162434 (Ensembl)
JUNGeneProductENSG00000177606 (Ensembl) NFKB not specified
MAP3K7GeneProductENSG00000135341 (Ensembl)
MAPK14GeneProductENSG00000112062 (Ensembl)
MAPK8GeneProductENSG00000107643 (Ensembl)
MYD88GeneProductENSG00000172936 (Ensembl)
NEMOGeneProductQ9Y6K9 (Uniprot-TrEMBL)
NFKBGeneProductENSG00000109320 (Ensembl) NFKB not specified
OAS1GeneProductENSG00000089127 (Ensembl)
OAS2GeneProductENSG00000111335 (Ensembl)
OAS3GeneProductENSG00000111331 (Ensembl)
PKRGeneProductENSG00000055332 (Ensembl)
PLpro (nsp3)GeneProductYP_009725299.1 (RefSeq)
STAT1GeneProductENSG00000115415 (Ensembl)
STAT2GeneProductENSG00000170581 (Ensembl)
TBK1GeneProductENSG00000183735 (Ensembl)
TLR7GeneProductENSG00000196664 (Ensembl)
TRAF3GeneProductENSG00000131323 (Ensembl)
TRAF6GeneProductENSG00000175104 (Ensembl)
TREML4GeneProductENSG00000188056 (Ensembl) TRAM not specified
TYK2GeneProductENSG00000105397 (Ensembl)

Annotated Interactions

No annotated interactions

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