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10.1038/s41467-020-18764-3

http://scihub22266oqcxt.onion/10.1038/s41467-020-18764-3
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suck abstract from ncbi


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pmid33009401      Nat+Commun 2020 ; 11 (1): 4938
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  • SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate #MMPMID33009401
  • Olagnier D; Farahani E; Thyrsted J; Blay-Cadanet J; Herengt A; Idorn M; Hait A; Hernaez B; Knudsen A; Iversen MB; Schilling M; Jorgensen SE; Thomsen M; Reinert LS; Lappe M; Hoang HD; Gilchrist VH; Hansen AL; Ottosen R; Nielsen CG; Moller C; van der Horst D; Peri S; Balachandran S; Huang J; Jakobsen M; Svenningsen EB; Poulsen TB; Bartsch L; Thielke AL; Luo Y; Alain T; Rehwinkel J; Alcami A; Hiscott J; Mogensen TH; Paludan SR; Holm CK
  • Nat Commun 2020[Oct]; 11 (1): 4938 PMID33009401show ga
  • Antiviral strategies to inhibit Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and the pathogenic consequences of COVID-19 are urgently required. Here, we demonstrate that the NRF2 antioxidant gene expression pathway is suppressed in biopsies obtained from COVID-19 patients. Further, we uncover that NRF2 agonists 4-octyl-itaconate (4-OI) and the clinically approved dimethyl fumarate (DMF) induce a cellular antiviral program that potently inhibits replication of SARS-CoV2 across cell lines. The inhibitory effect of 4-OI and DMF extends to the replication of several other pathogenic viruses including Herpes Simplex Virus-1 and-2, Vaccinia virus, and Zika virus through a type I interferon (IFN)-independent mechanism. In addition, 4-OI and DMF limit host inflammatory responses to SARS-CoV2 infection associated with airway COVID-19 pathology. In conclusion, NRF2 agonists 4-OI and DMF induce a distinct IFN-independent antiviral program that is broadly effective in limiting virus replication and in suppressing the pro-inflammatory responses of human pathogenic viruses, including SARS-CoV2.
  • |Adult[MESH]
  • |Anti-Inflammatory Agents/*pharmacology[MESH]
  • |Antioxidants/pharmacology[MESH]
  • |Antiviral Agents/*pharmacology[MESH]
  • |Betacoronavirus/*drug effects/metabolism[MESH]
  • |COVID-19[MESH]
  • |Coronavirus Infections/*drug therapy/virology[MESH]
  • |Dimethyl Fumarate/*agonists/pharmacology[MESH]
  • |Female[MESH]
  • |Gene Expression[MESH]
  • |Gene Knockdown Techniques[MESH]
  • |Humans[MESH]
  • |Interferon Type I[MESH]
  • |Lung/pathology[MESH]
  • |Male[MESH]
  • |NF-E2-Related Factor 2/genetics/*metabolism[MESH]
  • |Pandemics[MESH]
  • |Pneumonia, Viral/*drug therapy/virology[MESH]
  • |SARS-CoV-2[MESH]
  • |Signal Transduction/drug effects[MESH]
  • |Succinates/*agonists/pharmacology[MESH]


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