Role of Nuclear Factor Erythroid 2 (Nrf2) in the Recovery of Long COVID-19 Using Natural Antioxidants: A Systematic Review

Abstract

Coronavirus disease 2019 (COVID-19) is an infectious disease with approximately 517 million confirmed cases, with the average number of cases revealing that patients recover immediately without hospitalization. However, several other cases found that patients still experience various symptoms after 3–12 weeks, which is known as a long COVID syndrome. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can activate nuclear factor kappa beta (NF-κβ) and unbind the nuclear factor erythroid 2-related factor 2 (Nrf2) with Kelch-like ECH-associated protein 1 (Keap1), causing inhibition of Nrf2, which has an important role in antioxidant response and redox homeostasis. Disrupting the Keap1–Nrf2 pathway enhances Nrf2 activity, and has been identified as a vital approach for the prevention of oxidative stress and inflammation. Hence, natural antioxidants from various sources have been identified as a promising strategy to prevent oxidative stress, which plays a role in reducing the long COVID-19 symptoms. Oxygen-rich natural antioxidant compounds provide an effective Nrf2 activation effect that interact with the conserved amino acid residues in the Keap1-binding pocket, such as Ser602, Ser363, Ser508, and Ser555. In this review, the benefits of various natural antioxidant compounds that can modulate the Nrf2 signaling pathway, which is critical in reducing and curing long COVID-19, are highlighted and discussed.

Links between Vitamin K, Ferroptosis and SARS-CoV-2 Infection

“…The Nrf2 pathway is a cellular defense mechanism that helps protect cells from oxidative stress by upregulating the expression of genes involved in antioxidant defense and detoxification. Vitamin K 2 has been shown to activate this pathway, leading to increased expression of antioxidant enzymes, including glutathione peroxidase [ 130 , 131 , 132 ]. Given the potential role of ferroptosis in COVID-19 pathogenesis and the possible link between vitamin K and ferroptosis, there is interest in exploring the potential therapeutic benefits of vitamin K in COVID-19.…”

Green synthesis of multifunctional ZnO/chitosan nanocomposite film using wild Mentha pulegium extract for packaging applications

“…When cytokine storm hits, the afflicted victims die. A cytokine storm caused by a coronavirus can be prevented by several naturally occurring polyphenols, such as curcumin, apigenin, resveratrol, and kaempferol [70] , [71] , [72] , [73] , [74] . These findings suggest that edible antimicrobial coatings on fruits can help prevent virus transmission before infection, while also extending the shelf-life of polyphenolic fruits, which are vital for the recovery of COVID-19 patients.…”

Identification of dynamic gene expression profiles during sequential vaccination with ChAdOx1/BNT162b2 using machine learning methods

“…The protein synthesis of SARS-CoV-2 may increase Cys and activate endoplasmic reticulum stress of transcription factors, which ultimately promotes changes in cellular oxidation, cellular metabolism, and GSH transmembrane flux (Galli et al, 2022). Importantly, NRF2 activation has been shown to benefit respiratory infections in various animal models (Muchtaridi et al, 2022). NRF2 exerts anti-inflammatory effects by inhibiting pro-inflammatory genes such as IL6 and IL1B (Huang et al, 2022).…”