Antiviral and anti-inflammatory effects of Nrf2 on SARS-CoV-2 pathway (Homo sapiens)

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81011345, 9EndosomevasodilationProteolytic cleavageCytoplasmSARS-CoV-2Nucleus ReleaseHMOX1biliverdinhemeTMPRSS2ACE22.nucleocapsid uncoating3. Translation5. viral genome replication6. Subgenomic transription7. Translation of viral proteins8. Viral assemblyorf1orf1abPL2-PRO (nsp3)3CL-PRO(nsp5)nsp8nsp12nsp76, 11polymerasecomplexnsp7nsp8nsp12nsp87, 11NFE2L2KEAP1NFE2L2KEAP1PMAFARENFE2L2PTATA boxGenesPhase II enzymesGCLCHMOX1SLC7A11NQO1GSTA2GCLM14Viral Infection /Oxidative stressNRF2 targetgenesironCO9sGCGUCY1B2GUCY1A2GUCY1A3GUCY1B3GTPcGMPPKG2NOX1ROS99HYPERTENSIONSARS-CoV-21. Binding to ACE2 and viral entry via membrane fusion9.ExocytosisINF-I alpha/ betaIRF3HMOX1P9ISRERNARNAERGIC4. Proteolysis12PIKK-betaIKK-alphaIKK-gammaHSP90S32-PS36-Pp50p65I-Kappa-Bp65p5014inflammatory cytokinesinflammatory response1REIL-8MMP3CCL2TNF alphaIL-12IL-1 BetaMMP1IL-6


Description

Potential pathway for antiviral and anti-hypertensive effects of Nrf2 (Working progress)

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Ontology Terms

 

Bibliography

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  1. ''Chemistry and Biology of SARS-CoV-2.''; Chem, 2020 PubMed Europe PMC Scholia
  2. Gao Y, Yan L, Huang Y, Liu F, Zhao Y, Cao L, Wang T, Sun Q, Ming Z, Zhang L, Ge J, Zheng L, Zhang Y, Wang H, Zhu Y, Zhu C, Hu T, Hua T, Zhang B, Yang X, Li J, Yang H, Liu Z, Xu W, Guddat LW, Wang Q, Lou Z, Rao Z; ''Structure of the RNA-dependent RNA polymerase from COVID-19 virus.''; Science, 2020 PubMed Europe PMC Scholia
  3. ''Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant.''; J Transl Med, 2020 PubMed Europe PMC Scholia
  4. Chen Y, Liu Q, Guo D; ''Emerging coronaviruses: Genome structure, replication, and pathogenesis.''; J Med Virol, 2020 PubMed Europe PMC Scholia
  5. Deshmukh P, Unni S, Krishnappa G, Padmanabhan B; ''The Keap1-Nrf2 pathway: promising therapeutic target to counteract ROS-mediated damage in cancers and neurodegenerative diseases.''; Biophys Rev, 2017 PubMed Europe PMC Scholia
  6. ''cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action''; Pharmacol Rev., 2010 PubMed Europe PMC Scholia
  7. Singh D, Wasan H, Reeta KH.; ''Heme oxygenase-1 modulation: A potential therapeutic target for COVID-19 and associated complications.''; Free Radic Biol Med. , 2020 PubMed Europe PMC Scholia
  8. Wu L, Wang R; ''Carbon monoxide: endogenous production, physiological functions, and pharmacological applications.''; Pharmacol Rev, 2005 PubMed Europe PMC Scholia
  9. 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
  10. ''Remdesivir and SARS-CoV-2: Structural requirements at both nsp12 RdRp and nsp14 Exonuclease active-sites.''; Antiviral Res, 2020 PubMed Europe PMC Scholia
  11. Wu L, Wang R; ''Carbon monoxide: endogenous production, physiological functions, and pharmacological applications.''; Pharmacol Rev, 2005 PubMed Europe PMC Scholia
  12. Kim JE, You DJ, Lee C, Ahn C, Seong JY, Hwang JI; ''Suppression of NF-kappaB signaling by KEAP1 regulation of IKKbeta activity through autophagic degradation and inhibition of phosphorylation.''; Cell Signal, 2010 PubMed Europe PMC Scholia
  13. Ryter SW, Choi AM; ''Heme oxygenase-1/carbon monoxide: from metabolism to molecular therapy.''; Am J Respir Cell Mol Biol, 2009 PubMed Europe PMC Scholia
  14. Ramezani A, Nahad MP, Faghihloo E; ''The role of Nrf2 transcription factor in viral infection.''; J Cell Biochem, 2018 PubMed Europe PMC Scholia
  15. ''Structure of replicating SARS-CoV-2 polymerase.''; Nature, 2020 PubMed Europe PMC Scholia
  16. ''The nuclear factor NF-kappaB pathway in inflammation ''; Cold Spring Harb Perspect Biol., 2009 PubMed Europe PMC Scholia
  17. ''Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2.''; Science, 2020 PubMed Europe PMC Scholia
  18. Ahmed SM, Luo L, Namani A, Wang XJ, Tang X; ''Nrf2 signaling pathway: Pivotal roles in inflammation.''; Biochim Biophys Acta Mol Basis Dis, 2017 PubMed Europe PMC Scholia
  19. Wardyn JD, Ponsford AH, Sanderson CM; ''Dissecting molecular cross-talk between Nrf2 and NF-κB response pathways''; Biochem Soc Trans 43:621–626., 2015 PubMed Europe PMC Scholia
  20. Cuadrado A, Pajares M, Benito C, Jiménez-Villegas J, Escoll M, Fernández-Ginés R, Garcia Yagüe AJ, Lastra D, Manda G, Rojo AI, Dinkova-Kostova AT; ''Can Activation of NRF2 Be a Strategy against COVID-19?''; Trends Pharmacol Sci, 2020 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
125765view14:36, 9 March 2023DeSlRedrew GTP to cGMP conversion, hoping to solve Jenkins issues
125752view10:24, 9 March 2023DeSlChanged pathway node to textLabels (since these did not describe PWs), and tried to fix GTP to cGMP conversion.
124660view13:38, 18 November 2022NhungPupdate viral proteins shapes
124625view08:02, 18 November 2022NhungPupdate viral protein color
124429view12:41, 27 October 2022Mkutmonfix labels of data nodes
119486view14:16, 2 July 2021RTokaai
119485view13:44, 2 July 2021RTokaai
119477view08:49, 1 July 2021Mkutmonupdated layout
119435view03:24, 29 June 2021RTokaai
119434view01:55, 29 June 2021RTokaai
119433view01:51, 29 June 2021RTokaaiChanged format of pathway
119224view17:35, 22 June 2021RTokaai
119223view17:29, 22 June 2021RTokaaiChange font size
119222view17:22, 22 June 2021RTokaaiOntology Term : 'DOID:10763' removed !
119221view17:20, 22 June 2021RTokaaiChange titel name and changed interactions
119092view06:59, 17 June 2021RTokaaiincreased font size and removed interaction between cGMP and hypertension
118991view10:53, 7 June 2021Mkutmonupdated description
118990view10:52, 7 June 2021Mkutmonupdate title
118811view07:51, 2 June 2021Mkutmonremove wrong nfkb label
118809view07:50, 2 June 2021MkutmonOntology Term : 'nuclear factor, erythroid 2 like 2 signaling pathway' added !
118807view07:50, 2 June 2021MkutmonOntology Term : 'hypertension' added !
118806view07:49, 2 June 2021MkutmonOntology Term : 'COVID-19' added !
118805view07:49, 2 June 2021Mkutmonfixed references
118804view07:47, 2 June 2021Mkutmonfix publication references
118792view03:05, 2 June 2021RTokaaiIncluded literature and interplay between NRF2 and NF-kB
118665view03:55, 1 June 2021RTokaaiAdded literature references
118578view13:36, 28 May 2021EweitzModified title
118573view12:23, 28 May 2021RTokaaiNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
1. Binding to ACE2 and viral entry via membrane fusionPathway
2.nucleocapsid uncoatingPathway
3. TranslationPathway
3CL-PRO(nsp5)ProteinQ87917582 (Wikidata)
4. ProteolysisPathway
5. viral genome replicationPathway
6. Subgenomic transriptionPathway
7. Translation of viral proteinsPathway
8. Viral assemblyPathway
9.ExocytosisPathway
ACE2GeneProduct59272 (Entrez Gene)
CCL2GeneProduct6347 (Entrez Gene)
COMetabolite17245 (ChEBI)
GCLCGeneProduct2729 (Entrez Gene)
GCLMGeneProduct2730 (Entrez Gene)
GSTA2GeneProduct2939 (Entrez Gene)
GTPMetaboliteCHEBI:37565 (ChEBI)
GUCY1A2GeneProductENSG00000152402 (Ensembl)
GUCY1A3GeneProductENSG00000164116 (Ensembl)
GUCY1B2GeneProductENSG00000123201 (Ensembl)
GUCY1B3GeneProductENSG00000061918 (Ensembl)
HMOX1GeneProduct3162 (Entrez Gene)
HSP90GeneProduct3320 (Entrez Gene)
I-Kappa-BGeneProductENSG00000100906 (Ensembl)
IKK-alphaGeneProductENSG00000213341 (Ensembl)
IKK-betaGeneProductENSG00000104365 (Ensembl)
IKK-gammaGeneProductENSG00000269335 (Ensembl)
IL-1 BetaGeneProductENSG00000125538 (Ensembl)
IL-12GeneProductIL12A (HGNC)
IL-6GeneProductENSG00000136244 (Ensembl)
IL-8GeneProductENSG00000169429 (Ensembl)
INF-I alpha/ betaProteinQ6046488 (Wikidata)
IRF3GeneProductENSG00000126456 (Ensembl)
KEAP1GeneProductENSG00000079999 (Ensembl)
MAFGeneProductENSG00000186350 (Ensembl)
MMP1GeneProductENSG00000196611 (Ensembl)
MMP3GeneProductENSG00000149968 (Ensembl)
NFE2L2GeneProductENSG00000116044 (Ensembl)
NOX1GeneProductENSG00000007952 (Ensembl)
NQO1GeneProduct1728 (Entrez Gene)
PKG2GeneProductENSG00000138669 (Ensembl)
PL2-PRO (nsp3)ProteinQ87917581 (Wikidata) nsp3
RNARnaQ82069695 (Wikidata)
ROSMetaboliteCHEBI:26523 (ChEBI)
SLC7A11GeneProductENSG00000151012 (Ensembl)
TMPRSS2GeneProductENSG00000184012 (Ensembl)
TNF alphaGeneProductENSG00000232810 (Ensembl)
biliverdinMetabolite17033 (ChEBI)
cGMPMetaboliteCHEBI:16356 (ChEBI)
hemeMetaboliteHMDB03178 (HMDB)
ironMetabolite29033 (ChEBI)
nsp12ProteinQ94647436 (Wikidata) RdRp
nsp7ProteinQ90038963 (Wikidata)
nsp8ProteinQ88659350 (Wikidata)
orf1GeneProduct43740578 (Entrez Gene)
orf1abProteinP0DTD1 (Uniprot-TrEMBL)
p50GeneProductENSG00000109320 (Ensembl)
p65GeneProductENSG00000173039 (Ensembl)
polymerase complexComplexCPX-5742 (Complex Portal)

Annotated Interactions

No annotated interactions

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