Erdosteine inhibits viral infection and modulates innate immunity and stress oxidative state in RSV-infected A549 cell

<bold>Background:</bold> Glutathione (GSH) depletion characterizes several viral infections and various molecules have been suggested to restore GSH levels. Erdosteine (ERD) seems to be useful in treating patients with these infections such as respiratory syncytial virus (RSV). <bold>Aims:</bold> The main objective was to evaluate effects of ERD in RSV in vitro infection. Then we investigated the RSV-infected cell transcriptome to speculate on molecular pathways involved in ERD antiviral mechanism. We focused on the innate immune pathways of type 1 Interferon (IFN). Glutathione pathway was analysed to understand the impact on oxidative stress, as well. <bold>Methods:</bold> Viral infection assay on A549 cell line has been set up adding ERD at 100mg/mL and 1000mg/mL after infection with hRSV A2001/3-12 at concentration of 1.26 TCID50/µL. Viral replication in culture supernatant was assessed by qPCR at 48h post-infection (hpi). At 72hpi innate immune response signaling and oxidative stress pathway were analyzed using RT-PCR custom-array with a set of 60 optimized primer assays. <bold>Results:</bold> Post-treatment with ERD 1000µg/mL resulted in a statistically significant antiviral effect (p= 0.002) against RSV. Infected cells treated with ERD displayed an overexpression of innate immunity (IFITM1, IFITM3) and oxidative stress (GPX2) components. Interestingly, a decrease in expression level of CASP1, CASP4, CCL2, CXCL2, DDX58, ICAM1, IFNAR1, IL1B, IL8, IL6, ISG20, NFKB1, AHR, GPX3, and SOD2 was observed. <bold>Conclusions:</bold> ERD modulates several molecular pathways involved in induction of anti-viral state. The upregulation of some ISGs and reduction of pro-inflammatory cytokines suggest ERD as adjuvant in respiratory viral infections.