Entry Name Coronavirus disease - COVID-19
Description Coronavirus disease of 2019 (COVID-19) is a highly contagious respiratory infection that is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infects alveolar epithelial cells [mainly alveolar epithelial type 2 (AEC2) cells] through the angiotensin-converting enzyme 2 (ACE2) receptor. Upon the occupancy of ACE2 by SARS-CoV-2, the increased serum level of free Angiotensin II (Ang II) due to a reduction of ACE2-mediated degradation promotes activation of the NF-kappa B pathway via Ang II type 1 receptor (AT1R), followed by interleukin-6 (IL-6) production. SARS-CoV-2 also activates the innate immune system; macrophage stimulation triggers the overproduction of pro-inflammatory cytokines, including IL-6, and the "cytokine storm", which results in systemic inflammatory response syndrome and multiple organ failure. The combined effects of complement activation, dysregulated neutrophilia, endothelial injury, and hypercoagulability appear to be intertwined to drive the severe features of COVID-19.
Class Human Diseases; Infectious disease: viralBRITE hierarchy
Pathway map ko05171 Coronavirus disease - COVID-19
Ortholog table Disease Drug D03506 Cinanserin hydrochloride (USAN)
D11943 Molnupiravir (JAN/USAN)
D12115 COVID-19 vaccine (ChAdOx1-S [recombinant])
D12129 COVID-19 vaccine (Ad26.COV2-S [recombinant])
D12142 Casirivimab and imdevimab
D12244 Nirmatrelvir (JAN/USAN)
D12260 Bemnifosbuvir sulfate (USAN)
D12336 SARS-CoV-2 Spike glycoprotein vaccine antigen nvx-cov2373
D12353 Ensitrelvir fumarate (USAN)
D12389 Adintrevimab (USAN/INN)
D12778 Olgotrelvir sodium (USAN)
Orthology K25011 SARS coronavirus host translation inhibitor nsp1
K25012 SARS coronavirus non-structural protein 2
K25014 SARS coronavirus non-structural protein 4
K25016 SARS coronavirus non-structural protein 6
K25017 SARS coronavirus non-structural protein 7
K25018 SARS coronavirus non-structural protein 8
K25019 SARS coronavirus non-structural protein 9
K25020 SARS coronavirus non-structural protein 10
K25023 SARS coronavirus proofreading exoribonuclease [EC:3.1.13.-]
K25024 SARS coronavirus uridylate-specific endoribonuclease
K25025 SARS coronavirus 2'-O-methyltransferase [EC:2.1.1.-]
K24152 SARS coronavirus spike glycoprotein
K24151 SARS coronavirus envelope small membrane protein
K24150 SARS coronavirus membrane protein
K24106 SARS coronavirus nucleocapsid protein
K24579 SARS coronavirus accessory protein 3a
K24580 SARS coronavirus accessory protein 6
K24581 SARS coronavirus accessory protein 7a
K24582 SARS coronavirus accessory protein 7b
K24583 SARS coronavirus accessory protein 8
K24584 SARS coronavirus accessory protein 10
K04166 angiotensin II receptor type 1
K21421 NADPH oxidase 2 [EC:1.-.-.-]
K02580 nuclear factor NF-kappa-B p105 subunit
K04735 transcription factor p65
K03156 tumor necrosis factor superfamily, member 2
K01394 matrix metalloproteinase-3 (stromelysin 1, progelatinase) [EC:3.4.24.17 ]
K01388 matrix metalloproteinase-1 (interstitial collagenase) [EC:3.4.24.7 ]
K06059 disintegrin and metalloproteinase domain-containing protein 17 [EC:3.4.24.86 ]
K03158 tumor necrosis factor receptor superfamily member 1A
K04734 NF-kappa-B inhibitor alpha
K02581 NF-kappa-B inhibitor beta
K08523 heparin-binding EGF-like growth factor
K05060 interleukin 6 signal transducer
K04692 signal transducer and activator of transcription 3
K05423 granulocyte colony-stimulating factor
K05427 granulocyte-macrophage colony-stimulating factor
K12671 C-X-C motif chemokine 10
K02981 small subunit ribosomal protein S2e
K02985 small subunit ribosomal protein S3e
K02984 small subunit ribosomal protein S3Ae
K02987 small subunit ribosomal protein S4e
K02989 small subunit ribosomal protein S5e
K02991 small subunit ribosomal protein S6e
K02993 small subunit ribosomal protein S7e
K02995 small subunit ribosomal protein S8e
K02997 small subunit ribosomal protein S9e
K02947 small subunit ribosomal protein S10e
K02949 small subunit ribosomal protein S11e
K02951 small subunit ribosomal protein S12e
K02953 small subunit ribosomal protein S13e
K02955 small subunit ribosomal protein S14e
K02958 small subunit ribosomal protein S15e
K02957 small subunit ribosomal protein S15Ae
K02960 small subunit ribosomal protein S16e
K02962 small subunit ribosomal protein S17e
K02964 small subunit ribosomal protein S18e
K02966 small subunit ribosomal protein S19e
K02969 small subunit ribosomal protein S20e
K02971 small subunit ribosomal protein S21e
K02973 small subunit ribosomal protein S23e
K02974 small subunit ribosomal protein S24e
K02975 small subunit ribosomal protein S25e
K02976 small subunit ribosomal protein S26e
K02978 small subunit ribosomal protein S27e
K02977 ubiquitin-small subunit ribosomal protein S27Ae
K02979 small subunit ribosomal protein S28e
K02980 small subunit ribosomal protein S29e
K02983 small subunit ribosomal protein S30e
K02998 small subunit ribosomal protein SAe
K02925 large subunit ribosomal protein L3e
K02930 large subunit ribosomal protein L4e
K02932 large subunit ribosomal protein L5e
K02934 large subunit ribosomal protein L6e
K02937 large subunit ribosomal protein L7e
K02936 large subunit ribosomal protein L7Ae
K02938 large subunit ribosomal protein L8e
K02940 large subunit ribosomal protein L9e
K02866 large subunit ribosomal protein L10e
K02865 large subunit ribosomal protein L10Ae
K02868 large subunit ribosomal protein L11e
K02870 large subunit ribosomal protein L12e
K02873 large subunit ribosomal protein L13e
K02872 large subunit ribosomal protein L13Ae
K02875 large subunit ribosomal protein L14e
K02877 large subunit ribosomal protein L15e
K02880 large subunit ribosomal protein L17e
K02883 large subunit ribosomal protein L18e
K02882 large subunit ribosomal protein L18Ae
K02885 large subunit ribosomal protein L19e
K02889 large subunit ribosomal protein L21e
K02891 large subunit ribosomal protein L22e
K02894 large subunit ribosomal protein L23e
K02893 large subunit ribosomal protein L23Ae
K02896 large subunit ribosomal protein L24e
K02898 large subunit ribosomal protein L26e
K02901 large subunit ribosomal protein L27e
K02900 large subunit ribosomal protein L27Ae
K02903 large subunit ribosomal protein L28e
K02905 large subunit ribosomal protein L29e
K02908 large subunit ribosomal protein L30e
K02910 large subunit ribosomal protein L31e
K02912 large subunit ribosomal protein L32e
K02915 large subunit ribosomal protein L34e
K02918 large subunit ribosomal protein L35e
K02917 large subunit ribosomal protein L35Ae
K02920 large subunit ribosomal protein L36e
K02922 large subunit ribosomal protein L37e
K02921 large subunit ribosomal protein L37Ae
K02923 large subunit ribosomal protein L38e
K02924 large subunit ribosomal protein L39e
K02927 ubiquitin-large subunit ribosomal protein L40e
K02928 large subunit ribosomal protein L41e
K02929 large subunit ribosomal protein L44e
K02941 large subunit ribosomal protein LP0
K02942 large subunit ribosomal protein LP1
K02943 large subunit ribosomal protein LP2
K06856 immunoglobulin heavy chain
K06472 low affinity immunoglobulin gamma Fc receptor II-a
K00922 phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K02649 phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K04729 myeloid differentiation primary response protein MyD88
K04440 mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24 ]
K04379 proto-oncogene protein c-fos
K04448 transcription factor AP-1
K04467 inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10 ]
K07209 inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10 ]
K07210 inhibitor of nuclear factor kappa-B kinase subunit gamma
K12800 NACHT, LRR and PYD domains-containing protein 3
K12159 ubiquitin cross-reactive protein
K12647 interferon-induced helicase C domain-containing protein 1 [EC:5.6.2.6 ]
K12648 mitochondrial antiviral-signaling protein
K03174 TNF receptor-associated factor 3
K07211 inhibitor of nuclear factor kappa-B kinase subunit epsilon [EC:2.7.11.10 ]
K05411 interferon regulatory factor 3
K12654 stimulator of interferon genes protein
K11220 signal transducer and activator of transcription 1
K11221 signal transducer and activator of transcription 2
K04693 interferon regulatory factor 9
K14754 interferon-induced GTP-binding protein Mx
K16195 eukaryotic translation initiation factor 2-alpha kinase 2 [EC:2.7.11.1 ]
K04010 C5a anaphylatoxin chemotactic receptor 1
K04009 C3a anaphylatoxin chemotactic receptor
K03997 complement component 8 subunit alpha
K03998 complement component 8 subunit beta
K03999 complement component 8 subunit gamma
K03986 complement C1q subcomponent subunit A
K03987 complement C1q subcomponent subunit B
K03988 complement C1q subcomponent subunit C
K03992 mannan-binding lectin serine protease 1 [EC:3.4.21.-]
K03906 coagulation factor XIII B polypeptide
Compound Reference Authors Harrison AG, Lin T, Wang P
Title Mechanisms of SARS-CoV-2 Transmission and Pathogenesis.
Journal Reference Authors Perico L, Benigni A, Casiraghi F, Ng LFP, Renia L, Remuzzi G
Title Immunity, endothelial injury and complement-induced coagulopathy in COVID-19.
Journal Reference Authors Battagello DS, Dragunas G, Klein MO, Ayub ALP, Velloso FJ, Correa RG
Title Unpuzzling COVID-19: tissue-related signaling pathways associated with SARS-CoV-2 infection and transmission.
Journal Reference Authors Felsenstein S, Herbert JA, McNamara PS, Hedrich CM
Title COVID-19: Immunology and treatment options.
Journal Reference Authors Hojyo S, Uchida M, Tanaka K, Hasebe R, Tanaka Y, Murakami M, Hirano T
Title How COVID-19 induces cytokine storm with high mortality.
Journal Reference Authors Mahmudpour M, Roozbeh J, Keshavarz M, Farrokhi S, Nabipour I
Title COVID-19 cytokine storm: The anger of inflammation.
Journal Reference Authors Farooqi F, Dhawan N, Morgan R, Dinh J, Nedd K, Yatzkan G
Title Treatment of Severe COVID-19 with Tocilizumab Mitigates Cytokine Storm and Averts Mechanical Ventilation During Acute Respiratory Distress: A Case Report and Literature Review.
Journal Reference Authors Jamilloux Y, Henry T, Belot A, Viel S, Fauter M, El Jammal T, Walzer T, Francois B, Seve P
Title Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions.
Journal Reference Authors Kiselevskiy M, Shubina I, Chikileva I, Sitdikova S, Samoylenko I, Anisimova N, Kirgizov K, Suleimanova A, Gorbunova T, Varfolomeeva S
Title Immune Pathogenesis of COVID-19 Intoxication: Storm or Silence?
Journal Reference Authors Curran CS, Rivera DR, Kopp JB
Title COVID-19 Usurps Host Regulatory Networks.
Journal Reference Authors Quan C, Li C, Ma H, Li Y, Zhang H
Title Immunopathogenesis of Coronavirus-Induced Acute Respiratory Distress Syndrome (ARDS): Potential Infection-Associated Hemophagocytic Lymphohistiocytosis.
Journal Reference Authors Ahmed-Hassan H, Sisson B, Shukla RK, Wijewantha Y, Funderburg NT, Li Z, Hayes D Jr, Demberg T, Liyanage NPM
Title Innate Immune Responses to Highly Pathogenic Coronaviruses and Other Significant Respiratory Viral Infections.
Journal Reference Authors Tay MZ, Poh CM, Renia L, MacAry PA, Ng LFP
Title The trinity of COVID-19: immunity, inflammation and intervention.
Journal Reference Authors Xia H, Cao Z, Xie X, Zhang X, Chen JY, Wang H, Menachery VD, Rajsbaum R, Shi PY
Title Evasion of Type I Interferon by SARS-CoV-2.
Journal Reference Authors Hartenian E, Nandakumar D, Lari A, Ly M, Tucker JM, Glaunsinger BA
Title The molecular virology of coronaviruses.
Journal Reference Authors Amor S, Fernandez Blanco L, Baker D
Title Innate immunity during SARS-CoV-2: evasion strategies and activation trigger hypoxia and vascular damage.
Journal Reference Authors Catanzaro M, Fagiani F, Racchi M, Corsini E, Govoni S, Lanni C
Title Immune response in COVID-19: addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2.
Journal Reference Authors Jafarzadeh A, Chauhan P, Saha B, Jafarzadeh S, Nemati M
Title Contribution of monocytes and macrophages to the local tissue inflammation and cytokine storm in COVID-19: Lessons from SARS and MERS, and potential therapeutic interventions.
Journal Reference Authors Merad M, Martin JC
Title Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages.
Journal Reference Authors South AM, Tomlinson L, Edmonston D, Hiremath S, Sparks MA
Title Controversies of renin-angiotensin system inhibition during the COVID-19 pandemic.
Journal Reference Authors Furuhashi M, Moniwa N, Takizawa H, Ura N, Shimamoto K
Title Potential differential effects of renin-angiotensin system inhibitors on SARS-CoV-2 infection and lung injury in COVID-19.
Journal Reference Authors Gemmati D, Bramanti B, Serino ML, Secchiero P, Zauli G, Tisato V
Title COVID-19 and Individual Genetic Susceptibility/Receptivity: Role of ACE1/ACE2 Genes, Immunity, Inflammation and Coagulation. Might the Double X-chromosome in Females Be Protective against SARS-CoV-2 Compared to the Single X-Chromosome in Males?
Journal Reference Authors Kielian M
Title Enhancing host cell infection by SARS-CoV-2.
Journal Reference Authors Risitano AM, Mastellos DC, Huber-Lang M, Yancopoulou D, Garlanda C, Ciceri F, Lambris JD
Title Complement as a target in COVID-19?
Journal Reference Authors Noris M, Benigni A, Remuzzi G
Title The case of complement activation in COVID-19 multiorgan impact.
Journal Reference Authors Polycarpou A, Howard M, Farrar CA, Greenlaw R, Fanelli G, Wallis R, Klavinskis LS, Sacks S
Title Rationale for targeting complement in COVID-19.
Journal Reference Authors Teuwen LA, Geldhof V, Pasut A, Carmeliet P
Title COVID-19: the vasculature unleashed.
Journal Reference Authors Jodele S, Kohl J
Title Tackling COVID-19 infection through complement-targeted immunotherapy.
Journal Reference Authors Chauhan AJ, Wiffen LJ, Brown TP
Title COVID-19: A collision of complement, coagulation and inflammatory pathways.
Journal Reference Authors Colling ME, Kanthi Y
Title COVID-19-associated coagulopathy: An exploration of mechanisms.
Journal Reference Authors McFadyen JD, Stevens H, Peter K
Title The Emerging Threat of (Micro)Thrombosis in COVID-19 and Its Therapeutic Implications.
Journal Reference Authors Shi M, Wang L, Fontana P, Vora S, Zhang Y, Fu TM, Lieberman J, Wu H
Title SARS-CoV-2 Nsp1 suppresses host but not viral translation through a bipartite mechanism.
Journal Reference Authors Paniri A, Akhavan-Niaki H
Title Emerging role of IL-6 and NLRP3 inflammasome as potential therapeutic targets to combat COVID-19: Role of lncRNAs in cytokine storm modulation.
Journal Reference Authors Omarjee L, Janin A, Perrot F, Laviolle B, Meilhac O, Mahe G
Title Targeting T-cell senescence and cytokine storm with rapamycin to prevent severe progression in COVID-19.
Journal Reference Authors Zhang S, Li L, Shen A, Chen Y, Qi Z
Title Rational Use of Tocilizumab in the Treatment of Novel Coronavirus Pneumonia.
Journal Related ko04270 Vascular smooth muscle contraction
ko04610 Complement and coagulation cascades
ko04613 Neutrophil extracellular trap formation
ko04620 Toll-like receptor signaling pathway
ko04621 NOD-like receptor signaling pathway
ko04622 RIG-I-like receptor signaling pathway
ko04623 Cytosolic DNA-sensing pathway
ko04650 Natural killer cell mediated cytotoxicity
ko04666 Fc gamma R-mediated phagocytosis
ko04670 Leukocyte transendothelial migration
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