Author Correction: SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate

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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

Versiones preprint disponibles en: http://hdl.handle.net/10261/216920 y http://hdl.handle.net/10261/217161Antiviral 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.This research work was supported by Ester M og Konrad Kristian Sigurdssons Dyreværnsfond, Beckett-Fonden, Kong Christian IX og Dronning Louises Jubilæumslegat, Læge Sofus Carl Emil Friis og Hustru Olga Doris Friis´ legat, Købmand I Odense Johan og Hanne Weimann Født Seedorffs Legat, Hørslev Fonden, UK Medical Research Council (MRC core funding of the MRC Human Immunology Unit; JR), Lundbeck foundation (R303-2018-3379 and R219-2016-878, and R268-2016-3927), and Independent Research Fund Denmark – Medical Sciences (9039-00078B, 4004-00047B, and 0214-00001B). CarlsbergFoundation (Semper Ardens) and European Research Council (ERC-AdG ENVISION; 786602). Marie Skłodowska-Curie Action of the European Commission # 813343 and Italian Cancer Research Society #22891 to JH.Peer reviewe