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The Role of the NRF2 Pathway in the Pathogenesis of Viral Respiratory Infections

Daskou et al., Pathogens, doi:10.3390/pathogens13010039
Dec 2023  
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Curcumin for COVID-19
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Review discussing the role of the NRF2 antioxidant pathway in regulating viral replication and associated inflammation and cell damage pathways during respiratory viral infections. Authors summarize evidence showing that respiratory viruses like SARS-CoV-2, influenza, RSV, and rhinoviruses can either activate or inhibit NRF2 signaling, while NRF2 activation also impacts viral entry, replication, apoptosis, and ferroptosis. NRF2-induced heme oxygenase-1 in particular demonstrates antiviral properties against these viruses. Authors conclude that balancing physiologic NRF2 pathway activation holds therapeutic potential for ameliorating viral pathogenesis, and suggest NRF2 agonists like curcumin, sulforaphane, and epigallocatechin gallate may be beneficial as adjuvants for COVID-19 and other respiratory viral infections.
Reviews covering curcumin for COVID-19 include Arab, Daskou, Halma, Hegde, Hulscher, Kritis, Law, Rattis.
Daskou et al., 31 Dec 2023, peer-reviewed, 8 authors.
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The Role of the NRF2 Pathway in the Pathogenesis of Viral Respiratory Infections
Maria Daskou, Leila Fotooh Abadi, Chandrima Gain, Michael Wong, Eashan Sharma, Arnaud John Kombe Kombe, Ravikanth Nanduri, Theodoros Kelesidis
Pathogens, doi:10.3390/pathogens13010039
In humans, acute and chronic respiratory infections caused by viruses are associated with considerable morbidity and mortality. Respiratory viruses infect airway epithelial cells and induce oxidative stress, yet the exact pathogenesis remains unclear. Oxidative stress activates the transcription factor NRF2, which plays a key role in alleviating redox-induced cellular injury. The transcriptional activation of NRF2 has been reported to affect both viral replication and associated inflammation pathways. There is complex bidirectional crosstalk between virus replication and the NRF2 pathway because virus replication directly or indirectly regulates NRF2 expression, and NRF2 activation can reversely hamper viral replication and viral spread across cells and tissues. In this review, we discuss the complex role of the NRF2 pathway in the regulation of the pathogenesis of the main respiratory viruses, including coronaviruses, influenza viruses, respiratory syncytial virus (RSV), and rhinoviruses. We also summarize the scientific evidence regarding the effects of the known NRF2 agonists that can be utilized to alter the NRF2 pathway.
Informed Consent Statement: Not applicable.
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