ERS 2023: Erdostein and its Metabolite Met-1 Modulate Innate Immunity and Oxidative Stress in SARS-CoV-2 Infection
As part of the September congress of the European Respiratory Society (ERS 2023), the issue of COVID-19 was also addressed. Among the late-breaking messages was an e-poster by experts from the University of Milan, who in their study examined the potential of erdosteine and its active metabolite Met-1 in treating this disease, based on research into its application to cells infected with SARS-CoV-2.
Introduction
SARS-CoV-2, the causative agent of COVID-19, can cause a severe condition known as a 'cytokine storm' in infected patients, characterized by the overproduction of pro-inflammatory factors. Additionally, a glutathione deficiency is typical in the pathogenesis of SARS-CoV-2, leading to alterations in the redox state of cells and tissues infected with the virus. In this context, the antioxidant properties of erdosteine and its active metabolite Met-1 are of interest.
Methodology, Study Course, and Objectives
The aim of the cited study was to evaluate the effects of erdosteine and Met-1 on pathways of innate immunity mediated by type 1 interferons and inflammasomes in A549 cells infected with SARS-CoV-2. The researchers also analyzed the glutathione pathway to describe the effects on oxidative stress.
A viral infection test was first conducted on A549 cells by adding erdosteine or Met-1 in varying doses (100 μg/ml and 1000 μg/ml) after infecting them with SARS-CoV-2 (serotype B.1). After 72 hours post-infection, RNA was extracted and isolated from the cells. Innate immune response signaling pathways and oxidative stress were analyzed using a set of 60 optimized RT-PCR tests.
Results
Cells infected with SARS-CoV-2 and treated with 1000 μg/ml of both compounds showed overexpression of genes involved in oxidative stress processes and the glutathione pathway (GPX2, GUSB, CAT, PRDX5). Overexpression of interferon-stimulated genes and inflammasome components (CARD6, CASP1, CASP4, DDX58, IFNA1, and NLRP4) was also observed, along with a reduction in the expression level of interleukin 6 (IL-6).
Conclusion
Erdosteine and its active metabolite Met-1 activated the antiviral immune response by stimulating type 1 interferon and inflammasome pathways. Both molecules exhibited antioxidant effects that could delay or mitigate cellular damage, particularly through their ability to scavenge free radicals. These findings suggest that erdosteine and Met-1 may be effective in treating viral infections.
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Source: Strizzi S., Danzo F., Vanetti C. et al. Erdosteine and its metabolite Met-1 modulate innate immunity and oxidative stress in SARS-CoV-2 infection. e-poster, ID3854. ERS International Congress, Milan, 2023 Sep 9−13.
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