Surface different charge ligands for modulating selenium nanoparticles formation and activating the interaction with proteins for effective anti-Herpes simplex virus l infection.

Selenium-based nanoparticles exhibit antiviral activity by directly modulating immune function. Despite recent promising developments in utilizing selenium nanoparticles (Se NPs) against viral infections, the impact of surface ligand charge on the conformation and interaction with viral proteins, as well as the effectiveness of Se NPs in anti-Herpes simplex virus 1 (HSV-1) infection remains unexplored. In this study, three types of selenium nanoparticles (CTAB-Se, PVP-Se, SDS-Se) with distinct surface charges were synthesized by modifying the surface ligands. We found that apart from differences in surface charge, the size, morphology, and crystal structure of the three types of Se NPs were similar. Notably, although the lipophilicity and cellular uptake of SDS-Se with a negative charge were lower compared to positively charged CTAB-Se and neutrally charged PVP-Se, SDS-Se exhibited the strongest protein binding force during interaction with HSV-1. Consequently, SDS-Se demonstrated the most potent anti-HSV-1 activity and safeguarded normal cells from damage. The mechanistic investigation further revealed that SDS-Se NPs effectively inhibited the proliferation and assembly of HSV-1 by powerfully suppressing the key genes and proteins of HSV-1 at various stages of viral development. Hence, this study highlights the significant role of surface ligand engineering in the antiviral activity of Se NPs, presenting a viable approach for synthesizing Se NPs with tailored antiviral properties by modulating surface charge. This method holds promise for advancing research on the antiviral capabilities of Se NPs.