SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate.
Nat Commun
; 11(1): 4938, 2020 10 02.
Artículo
en Inglés
| MEDLINE | ID: covidwho-811574
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.
Texto completo:
Disponible
Colección:
Bases de datos internacionales
Base de datos:
MEDLINE
Asunto principal:
Antivirales
/
Neumonía Viral
/
Succinatos
/
Infecciones por Coronavirus
/
Factor 2 Relacionado con NF-E2
/
Dimetilfumarato
/
Betacoronavirus
/
Antiinflamatorios
Tipo de estudio:
Estudio pronóstico
Tópicos:
Vacunas
Límite:
Adulto
/
Femenino
/
Humanos
/
Masculino
Idioma:
Inglés
Revista:
Nat Commun
Asunto de la revista:
Biologia
/
Ciencia
Año:
2020
Tipo del documento:
Artículo
País de afiliación:
S41467-020-18764-3
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