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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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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, Vajdi, Yong.

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1. Arab et al., Immunoregulatory effects of nanocurcumin in inflammatory milieu: Focus on COVID-19, Biomedicine & Pharmacotherapy, doi:10.1016/j.biopha.2024.116131.sciencedirect.com, doi.org.

2. Daskou et al., The Role of the NRF2 Pathway in the Pathogenesis of Viral Respiratory Infections, Pathogens, doi:10.3390/pathogens13010039.mdpi.com, doi.org.

3. Halma et al., Exploring autophagy in treating SARS-CoV-2 spike protein-related pathology, Endocrine and Metabolic Science, doi:10.1016/j.endmts.2024.100163.sciencedirect.com, doi.org.

4. Hegde et al., Curcumin Formulations for Better Bioavailability: What We Learned from Clinical Trials Thus Far?, ACS Omega, doi:10.1021/acsomega.2c07326.acs.org, doi.org.

5. Hulscher et al., Clinical Approach to Post-acute Sequelae After COVID-19 Infection and Vaccination, Cureus, doi:10.7759/cureus.49204.cureus.com, doi.org.

6. Kritis et al., The combination of bromelain and curcumin as an immune-boosting nutraceutical in the prevention of severe COVID-19, Metabolism Open, doi:10.1016/j.metop.2020.100066.sciencedirect.com, doi.org.

7. Law et al., Photodynamic Action of Curcumin and Methylene Blue against Bacteria and SARS-CoV-2—A Review, Pharmaceuticals, doi:10.3390/ph17010034.mdpi.com, doi.org.

8. Rattis et al., Curcumin as a Potential Treatment for COVID-19, Frontiers in Pharmacology, doi:10.3389/fphar.2021.675287.frontiersin.org, doi.org.

9. Vajdi et al., Effect of polyphenols against complications of COVID-19: current evidence and potential efficacy, Pharmacological Reports, doi:10.1007/s43440-024-00585-6.springer.com, doi.org.

10. Yong et al., Natural Products-Based Inhaled Formulations for Treating Pulmonary Diseases, International Journal of Nanomedicine, doi:10.2147/ijn.s451206.dovepress.com, doi.org.

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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