Back to Search
Start Over
SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate
- Source :
- Olagnier , D P C , Farahani , E , Jensen , J T , Blay Cadanet , J , Herengt , A A P V , Idorn , M , Schneider Hait , A I , Hernaez , B , Knudsen , A , Iversen , M B , Schilling , M , Jørgensen , S E , Thomsen , M M , Reinert , L S , Lappe , M , Hoang , H D , Gilchrist , V H , Hansen , A L , Ottosen , R , Nielsen , C G , Møller , C , van der Horst , D , Peri , S , Balachandran , S , Huang , J , Jakobsen , M , Svenningsen , E B , Poulsen , T B , Bartsch , L , Thielke , A L , Luo , Y , Alain , T , Rehwinkel , J , Alcamí , A , Hiscott , J , Mogensen , T H , Paludan , S R & Holm , C K 2020 , ' SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate ' , Nature Communications , vol. 11 , 4938 .
- Publication Year :
- 2020
-
Abstract
- 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.
Details
- Database :
- OAIster
- Journal :
- Olagnier , D P C , Farahani , E , Jensen , J T , Blay Cadanet , J , Herengt , A A P V , Idorn , M , Schneider Hait , A I , Hernaez , B , Knudsen , A , Iversen , M B , Schilling , M , Jørgensen , S E , Thomsen , M M , Reinert , L S , Lappe , M , Hoang , H D , Gilchrist , V H , Hansen , A L , Ottosen , R , Nielsen , C G , Møller , C , van der Horst , D , Peri , S , Balachandran , S , Huang , J , Jakobsen , M , Svenningsen , E B , Poulsen , T B , Bartsch , L , Thielke , A L , Luo , Y , Alain , T , Rehwinkel , J , Alcamí , A , Hiscott , J , Mogensen , T H , Paludan , S R & Holm , C K 2020 , ' SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate ' , Nature Communications , vol. 11 , 4938 .
- Notes :
- application/pdf, English
- Publication Type :
- Electronic Resource
- Accession number :
- edsoai.on1322750523
- Document Type :
- Electronic Resource