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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

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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. / Olagnier, David; Farahani, Ensieh; Thyrsted, Jacob; Blay-Cadanet, Julia; Herengt, Angela; Idorn, Manja; Hait, Alon; Hernaez, Bruno; Knudsen, Alice; Iversen, Marie Beck; Schilling, Mirjam; Jørgensen, Sofie E; Thomsen, Michelle; Reinert, Line S; Lappe, Michael; Hoang, Huy-Dung; Gilchrist, Victoria H; Hansen, Anne Louise; Ottosen, Rasmus; Nielsen, Camilla G; Møller, Charlotte; van der Horst, Demi; 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; Hiscott, John; Mogensen, Trine H.; Paludan, Søren R; Holm, Christian K.

In: Nature Communications, Vol. 11, No. 1, 4938, 10.2020.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Harvard

Olagnier, D, Farahani, E, Thyrsted, J, Blay-Cadanet, J, Herengt, A, Idorn, M, Hait, A, Hernaez, B, Knudsen, A, Iversen, MB, Schilling, M, Jørgensen, SE, Thomsen, M, Reinert, LS, Lappe, M, Hoang, H-D, Gilchrist, VH, Hansen, AL, Ottosen, R, Nielsen, CG, Møller, 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, Alcamí, A, Hiscott, J, Mogensen, TH, Paludan, SR & Holm, CK 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, no. 1, 4938. https://doi.org/10.1038/s41467-020-18764-3

APA

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, 11(1), [4938]. https://doi.org/10.1038/s41467-020-18764-3

CBE

Olagnier D, Farahani E, Thyrsted J, Blay-Cadanet J, Herengt A, Idorn M, Hait A, Hernaez B, Knudsen A, Iversen MB, Schilling M, Jørgensen SE, Thomsen M, Reinert LS, Lappe M, Hoang H-D, Gilchrist VH, Hansen AL, Ottosen R, Nielsen CG, Møller 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, Alcamí A, Hiscott J, Mogensen TH, Paludan SR, Holm CK. 2020. SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate. Nature Communications. 11(1):Article 4938. https://doi.org/10.1038/s41467-020-18764-3

MLA

Olagnier, David et al. "SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate". Nature Communications. 2020. 11(1). https://doi.org/10.1038/s41467-020-18764-3

Vancouver

Olagnier D, Farahani E, Thyrsted J, Blay-Cadanet J, Herengt A, Idorn M et al. SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate. Nature Communications. 2020 Oct;11(1). 4938. https://doi.org/10.1038/s41467-020-18764-3

Author

Olagnier, David ; Farahani, Ensieh ; Thyrsted, Jacob ; Blay-Cadanet, Julia ; Herengt, Angela ; Idorn, Manja ; Hait, Alon ; Hernaez, Bruno ; Knudsen, Alice ; Iversen, Marie Beck ; Schilling, Mirjam ; Jørgensen, Sofie E ; Thomsen, Michelle ; Reinert, Line S ; Lappe, Michael ; Hoang, Huy-Dung ; Gilchrist, Victoria H ; Hansen, Anne Louise ; Ottosen, Rasmus ; Nielsen, Camilla G ; Møller, Charlotte ; van der Horst, Demi ; 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 ; Hiscott, John ; Mogensen, Trine H. ; Paludan, Søren R ; Holm, Christian K. / SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate. In: Nature Communications. 2020 ; Vol. 11, No. 1.

Bibtex

@article{3186bbcd508f49c4981dbb873ec17e05,
title = "SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate",
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.",
author = "David Olagnier and Ensieh Farahani and Jacob Thyrsted and Julia Blay-Cadanet and Angela Herengt and Manja Idorn and Alon Hait and Bruno Hernaez and Alice Knudsen and Iversen, {Marie Beck} and Mirjam Schilling and J{\o}rgensen, {Sofie E} and Michelle Thomsen and Reinert, {Line S} and Michael Lappe and Huy-Dung Hoang and Gilchrist, {Victoria H} and Hansen, {Anne Louise} and Rasmus Ottosen and Nielsen, {Camilla G} and Charlotte M{\o}ller and {van der Horst}, Demi and Suraj Peri and Siddharth Balachandran and Jinrong Huang and Martin Jakobsen and Svenningsen, {Esben B} and Poulsen, {Thomas B} and Lydia Bartsch and Thielke, {Anne L} and Yonglun Luo and Tommy Alain and Jan Rehwinkel and Antonio Alcam{\'i} and John Hiscott and Mogensen, {Trine H.} and Paludan, {S{\o}ren R} and Holm, {Christian K}",
year = "2020",
month = oct,
doi = "10.1038/s41467-020-18764-3",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate

AU - Olagnier, David

AU - Farahani, Ensieh

AU - Thyrsted, Jacob

AU - Blay-Cadanet, Julia

AU - Herengt, Angela

AU - Idorn, Manja

AU - Hait, Alon

AU - Hernaez, Bruno

AU - Knudsen, Alice

AU - Iversen, Marie Beck

AU - Schilling, Mirjam

AU - Jørgensen, Sofie E

AU - Thomsen, Michelle

AU - Reinert, Line S

AU - Lappe, Michael

AU - Hoang, Huy-Dung

AU - Gilchrist, Victoria H

AU - Hansen, Anne Louise

AU - Ottosen, Rasmus

AU - Nielsen, Camilla G

AU - Møller, Charlotte

AU - van der Horst, Demi

AU - Peri, Suraj

AU - Balachandran, Siddharth

AU - Huang, Jinrong

AU - Jakobsen, Martin

AU - Svenningsen, Esben B

AU - Poulsen, Thomas B

AU - Bartsch, Lydia

AU - Thielke, Anne L

AU - Luo, Yonglun

AU - Alain, Tommy

AU - Rehwinkel, Jan

AU - Alcamí, Antonio

AU - Hiscott, John

AU - Mogensen, Trine H.

AU - Paludan, Søren R

AU - Holm, Christian K

PY - 2020/10

Y1 - 2020/10

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-020-18764-3

DO - 10.1038/s41467-020-18764-3

M3 - Journal article

C2 - 33009401

VL - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 4938

ER -