SARS-CoV-2 infection and dysregulation of nuclear factor erythroid-2-related factor 2 (Nrf2) pathway

Rabab S Hamad; Hayder M Al-Kuraishy; Athanasios Alexiou; Marios Papadakis; Eman A Ahmed; Hebatallah M Saad; Gaber El-Saber Batiha

doi:10.1007/s12192-023-01379-0

SARS-CoV-2 infection and dysregulation of nuclear factor erythroid-2-related factor 2 (Nrf2) pathway

Cell Stress Chaperones. 2023 Nov;28(6):657-673. doi: 10.1007/s12192-023-01379-0. Epub 2023 Oct 5.

Authors

Rabab S Hamad^#^{1

2}, Hayder M Al-Kuraishy^#³, Athanasios Alexiou^{4

5}, Marios Papadakis⁶, Eman A Ahmed⁷, Hebatallah M Saad⁸, Gaber El-Saber Batiha⁹

Affiliations

¹ Biological Sciences Department, College of Science, King Faisal University, 31982, Al Ahsa, Saudi Arabia.
² Central Laboratory, Theodor Bilharz Research Institute, Giza, 12411, Egypt.
³ Department of Pharmacology, Toxicology and Medicine, Medical Faculty, College of Medicine, Al-Mustansiriyah University, P.O. Box 14132, Baghdad, Iraq.
⁴ Department of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, NSW, 2770, Australia.
⁵ AFNP Med, 1030, Vienna, Austria.
⁶ Department of Surgery II, University Hospital Witten-Herdecke, University of Witten-Herdecke, Heusnerstrasse 40, 42283, Wuppertal, Germany. marios_papadakis@yahoo.gr.
⁷ Department of Pharmacology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt.
⁸ Department of Pathology, Faculty of Veterinary Medicine, Matrouh University, Marsa Matruh, 51744, Egypt. heba.magdy@mau.edu.eg.
⁹ Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, Egypt. gaberbatiha@gmail.com.

^# Contributed equally.

Abstract

Coronavirus disease 2019 (COVID-19) is a recent pandemic caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) leading to pulmonary and extra-pulmonary manifestations due to the development of oxidative stress (OS) and hyperinflammation. The underlying cause for OS and hyperinflammation in COVID-19 may be related to the inhibition of nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of antioxidative responses and cellular homeostasis. The Nrf2 pathway inhibits the expression of pro-inflammatory cytokines and the development of cytokine storm and OS in COVID-19. Nrf2 activators can attenuate endothelial dysfunction (ED), renin-angiotensin system (RAS) dysregulation, immune thrombosis, and coagulopathy. Hence, this review aimed to reveal the potential role of the Nrf2 pathway and its activators in the management of COVID-19. As well, we tried to revise the mechanistic role of the Nrf2 pathway in COVID-19.

Keywords: COVID-19; Nuclear factor erythroid 2-related factor 2; Oxidative stress; SARS-CoV-2.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Humans
Lung
NF-E2-Related Factor 2
Renin-Angiotensin System
SARS-CoV-2

Substances

NF-E2-Related Factor 2