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Título: | SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate |
Autor: | Olagnier, David; Farahani, Ensieh; Thyrsted, Jacob; Blay-Cadanet, Julia; Herengt, Angela; Idorn, Manja; Hait, Alon; Hernáez, Bruno CSIC ORCID; Knudsen, Alice; Iversen, Marie Beck; Schilling, Mirjam; Jørgensen, Sofie E.; Thomsen, Michelle; Reinert, Line; Lappe, Michael; Hoang, Huy-Dung; Gilchrist, Victoria H.; Hansen, Anne Louise; Ottosen, Rasmus; Gunderstofte, Camilla; Møller, Charlotte; Horst, Demi van der; Peri, Suraj; Balachandran, Siddharth; Huang, Jinrong; Jakobsen, Martin; Svenningsen, Esben B.; Poulsen, Thomas B.; Bartsch, Lydia; Thielke, Anne L.; Luo, Yonglun; Alain, Tommy; Rehwinkel, Jan; Alcamí, Antonio CSIC ORCID; Hiscott, John; Mogensen, Trine; Paludan, Søren R.; Holm, Christian | Palabras clave: | Immunology Microbiology SARS-CoV-2 |
Fecha de publicación: | 2-oct-2020 | Editor: | Nature Publishing Group | Citación: | Nature Communications 11: 4938 (2020) | Resumen: | 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. | Descripción: | Versiones preprint disponibles en: http://hdl.handle.net/10261/216920 y http://hdl.handle.net/10261/217161 | Versión del editor: | https://doi.org/10.1038/s41467-020-18764-3 | URI: | http://hdl.handle.net/10261/220845 | DOI: | 10.1038/s41467-020-18764-3 | E-ISSN: | 2041-1723 |
Aparece en las colecciones: | (PTI Salud Global) Colección Especial COVID-19 (CBM) Artículos |
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SARS-CoV2-mediated suppression.pdf | 2,83 MB | Adobe PDF | Visualizar/Abrir |
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