Poly (allylamine hydrochloride)-selenium nanoparticles inhibit porcine reproductive and respiratory syndrome virus by targeting DDX5 and reactive oxygen species.

Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) remains a critical threat to the swine industry worldwide due to its rapid evolution and limited vaccine efficacy. In this study, we synthesized and characterized poly (allylamine hydrochloride)-selenium nanoparticles (PAH-Se NPs) and evaluated their antiviral activity against PRRSV in vitro and the underlying mechanism. PAH-Se NPs exhibited uniform spherical morphology with average hydrodynamic diameter of 118 nm and excellent colloidal stability with a zeta potential of +50.7 mV. Cytotoxicity assays demonstrated low toxicity of PAH-Se NPs in MARC-145 cells with a CC50 of 40.24 μg/mL, indicating favorable biocompatibility. Multiple complementary assays, including viral RNA quantification, cell viability restoration, plaque assays, N protein expression analyses, and indirect immunofluorescence assay, showed that PAH-Se NPs could significantly inhibit PRRSV replication in a dose-dependent manner, with an IC50 of 0.076 μg/mL. Moreover, this inhibition was equally effective against other sub-genotypes of PRRSV, including VR2332 and NADC30-like variants, as well as the DNA virus and bacteria, indicating the broad-spectrum anti-microbial properties of PAH-Se NPs. Mechanistic studies indicated that PAH-Se NPs target viral invasion and replication by down-regulating the host factor DDX5, which interacts with PRRSV Nsp9 to facilitate viral RNA synthesis, and suppressed PRRSV-induced reactive oxygen species (ROS) accumulation. This work emphasized PAH-Se NPs as a potent, low-toxicity antiviral candidate, offering promising potential for the development of alternative therapeutics against PRRSV and related viral infections.