Self-assembled cyanidin-3-O-glucoside nanoparticles alleviate inflammation and ferroptosis induced by PRRSV infection

Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly contagious pathogen that causes substantial economic losses in the global swine industry, primarily by impairing reproductive performance and respiratory health. However, current therapeutic approaches remain limited in effectively controlling PRRSV infection. Here, we present self-assembled cyanidin-3-O-glucoside (C3G)-based nanoparticles (C3G-Cs-SeNPs) as a promising antiviral agent against PRRSV infection. These nanoparticles demonstrated excellent stability and biocompatibility, with minimal cytotoxicity in Marc-145 cells. C3G-Cs-SeNPs significantly reduced ROS levels in PRRSV-infected cells, enhancing the antioxidant capacity and mitigating oxidative stress. In addition, they effectively inhibited key stages of the PRRSV lifecycle, including viral internalization and replication, leading to a marked decrease in viral proliferation. Moreover, C3G-Cs-SeNPs alleviated ferroptosis by restoring redox homeostasis through enhanced antioxidant enzyme activity. Mechanistically, these nanoparticles potentially activate the SIRT1/Nrf2/HO-1 signaling pathway, which plays a critical role in regulating inflammation and ferroptosis in PRRSV-infected cells. These findings suggest that C3G-Cs-SeNPs could serve as a novel therapeutic approach to modulate inflammation, ferroptosis, and viral replication in respiratory viral infections. Our study highlights the therapeutic potential of C3G-Cs-SeNPs in combating PRRSV infection, with important implications for viral infection management and respiratory disease treatment.IMPORTANCEPorcine reproductive and respiratory syndrome virus (PRRSV) remains a major challenge in the swine industry, causing significant economic losses due to its high mutation rate and ability to evade host immunity. Current antiviral treatments and vaccines offer limited efficacy, necessitating the development of novel therapeutic strategies. This study introduces self-assembled cyanidin-3-O-glucoside-based chitosan-selenium nanoparticles (C3G-Cs-SeNPs) as a promising antiviral agent. These nanoparticles effectively inhibit PRRSV replication, reduce oxidative stress, and alleviate inflammation and ferroptosis by activating the SIRT1/Nrf2/HO-1 signaling pathway. By mitigating virus-induced cellular damage, C3G-Cs-SeNPs offer a potential therapeutic approach for PRRSV and other respiratory viral infections. This study highlights the role of ferroptosis in PRRSV pathogenesis and presents an innovative nanotechnology-based solution to combat viral infections, contributing to the development of more effective antiviral strategies.