Potential Role of Antioxidant and Anti-Inflammatory Therapies to Prevent Severe SARS-Cov-2 Complications

Abstract

The coronavirus disease 2019 (COVID-19) pandemic is caused by a novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2). Here, we review the molecular pathogenesis of SARS-CoV-2 and its relationship with oxidative stress (OS) and inflammation. Furthermore, we analyze the potential role of antioxidant and anti-inflammatory therapies to prevent severe complications. OS has a potential key role in the COVID-19 pathogenesis by triggering the NOD-like receptor family pyrin domain containing 3 inflammasome and nuclear factor-kB (NF-kB). While exposure to many pro-oxidants usually induces nuclear factor erythroid 2 p45-related factor2 (NRF2) activation and upregulation of antioxidant related elements expression, respiratory viral infections often inhibit NRF2 and/or activate NF-kB pathways, resulting in inflammation and oxidative injury. Hence, the use of radical scavengers like N-acetylcysteine and vitamin C, as well as of steroids and inflammasome inhibitors, has been proposed. The NRF2 pathway has been shown to be suppressed in severe SARS-CoV-2 patients. Pharmacological NRF2 inducers have been reported to inhibit SARS-CoV-2 replication, the inflammatory response, and transmembrane protease serine 2 activation, which for the entry of SARS-CoV-2 into the host cells through the angiotensin converting enzyme 2 receptor. Thus, NRF2 activation may represent a potential path out of the woods in COVID-19 pandemic.

The Good and Bad of Nrf2: An Update in Cancer and New Perspectives in COVID-19

“…Activation of Nrf2 has been recently recognised as a possible tool to counteract inflammation and cytokine storms that occur under viral infections. In this context, some authors have highlighted the potential of Nrf2 activators for the treatment of coronavirus disease 19 (COVID-19) [ 7 , 8 ]. However, the benefits of stimulating Nrf2 mediated response against the viral disease need a better evaluation and further investigation.…”

The role of NADPH oxidases in infectious and inflammatory diseases

“…NOX2 activation is higher in COVID-19 patients compared to controls and higher in severe COVID-19 cases compared to non-severe cases [ 290 ]. Oxidative stress during SARS-CoV-2 infection may be due to activation of the NLRP3 inflammasome in infected cells [ 291 ]. It has been hypothesized that increased risk for oxidative stress and severe COVID-19 may be due to suppressed antioxidant responses through the NRF2 pathway, glutathione deficiency, or low levels of SOD3 expression in alveolar type II cells [ [291] , [292] , [293] ].…”

Therapeutic Potential of Alpha-Lipoic Acid in Viral Infections, including COVID-19

“…In addition, the Nrf2 pathway is suppressed in severe forms of SARS-CoV-2 infection, and, accordingly, the pharmacological inducers of Nrf2 are able to inhibit viral replication, the associated inflammatory response, and the activation of the transmembrane protease serine 2 (TMPRSS2), which is required for priming of the viral spike (S) protein and the subsequent virus–host cell membrane fusion and cell entry. Thus, Nrf2 activation may represent a new potential therapeutic approach for the COVID-19 pandemic [ 17 ].…”