Resveratrol; an inflammasome inhibitor and a potential therapy for severe cases of COVID-19

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 126 million people worldwide and deaths exceed two million. Virological features of SARS-CoV-2, including its genomic sequence, have been identified but the mechanisms governing coronavirus disease 2019 (COVID-19) immunopathogenesis have remained uncertain. Severe COVID-19 is associated with a cytokine storm, chronic inflammation, neutrophilia, lymphocyte dysfunction, lymphopenia, reduction in T-lymphocytes and natural killer (NK) cells, disruption in viral clearance, and neutrophil/macrophage infiltration in the lungs. In many cases, patients develop acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and/or multiple-organ dysfunction syndrome (MODS). Resveratrol reduces the expression of inflammasome activators such as thioredoxin-interacting protein (TXNIP) and nuclear factor erythroid 2 (NrF2) and increases that of the inflammasome inhibitor, i.e., NAD-dependent deacetylase sirtuin-1 (SIRT1). Resveratrol is able to inhibit the production of reactive oxygen species (ROS) and the activation of inducible nitric oxide synthases (iNOS). It affects signaling pathways including mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-ĸB) thereby further inhibiting inflammasomes. Because of its anti-inflammasome, anti-inflammatory, and anti-oxidant effects and considering the key role of inflammation and cytokine storm in disease severity and poor patient outcomes, it is concluded that resveratrol can be useful in the treatment of COVID-19. Given the persistence of the COVID-19 pandemic and the challenges of extensive vaccination in all countries, it is important to achieve more effective treatments to decrease the mortality rate and severity of severe injuries following COVID-19. Given all the effects reviewed in this article, resveratrol at a dose of up to 600 mg per day can be exploited as a potential adjunctive therapy for COVID-19 patients.

Single-cell RNA-seq public data reveal the gene regulatory network landscape of respiratory epithelial and peripheral immune cells in COVID-19 patients

“…SUN2 (Sad1 and UNC84 domain containing 2) is associated with mitosis, maintains a repressive chromatin state, and inhibits HIV-1 infection via association with Lamin A/C ( 47 , 48 ). Despite previous studies showing quercetin and resveratrol, inhibitors of thioredoxin-interacting protein (TXNIP), as potential therapies for COVID-19 ( 49 , 50 ), our observation of robust TXNIP downregulation in severe patients suggested that these inhibitors may exhibit reduced performance in these treatments to a certain degree.…”

Resveratrol regulates inflammation and improves oxidative stress via Nrf2 signaling pathway: Therapeutic and biotechnological prospects

“…Furthermore, it impeded inflammasomes by affecting signaling pathways such as nuclear factor kappa B (NF‐ĸB) and mitogen‐activated protein kinase (MAPK). Therefore, people who have COVID may benefit from taking RES as an additional treatment with the dose of up to 600 mg per day (Giordo, Zinellu, Eid, & Pintus, 2021; Mahmoudian‐Sani et al, 2022).…”

Integrated analyses of single-cell RNA-seq public data reveal the gene regulatory network landscape of respiratory epithelial and peripheral immune cells in COVID-19 patients

“…SUN2 (Sad1 and UNC84 domain containing 2) is associated with mitosis, it maintains a repressive chromatin state, and inhibits HIV-1 infection via association with Lamin A/C (45,46). Previous studies have also shown that quercetin and resveratrol, inhibitors of thioredoxin-interacting protein (TXNIP), could be considered as potential therapies for COVID-19 (47,48). However, we found that TXNIP showed robust downregulation in severe patients, which suggests that its inhibitors may provide a reduced performance in severe patient treatment to a certain degree.…”