The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate
Open accessAbstract
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.
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Metadata
- Authors
- Olagnier, D., Farahani, E., Thyrsted, J., Blay-Cadanet, J., Herengt, A., Idorn, M., Hait, A., Hernaez, B., Knudsen, A., Iversen, M. B., Schilling, M., Jørgensen, S. E., Thomsen, 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.
- Venue
- Nature Communications
- Published
- 2020-10-02
- Volume
- 11
- Issue
- 1
- Pages
- 4938-4938
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W3091428163
- Cited by
- 455
- References
- 50
- FWCI
- 9.23
- Type
- journal article
- Language
- en
- Open access
- gold
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- Olagnier, D., Farahani, E., Thyrsted, J., Blay-Cadanet, J., Herengt, A., Idorn, M., Hait, A., Hernaez, B., Knudsen, A., Iversen, M. B., Schilling, M., Jørgensen, S. E., Thomsen, M., Reinert, L. S., Lappe, M., Hoang, H.-D., Gilchrist, V. H., Hansen, A. L., Ottosen, 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. https://doi.org/10.1038/s41467-020-18764-3
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
