Photoinduced Cleavage of Respiratory Syncytial Virus by Chiral Vanadium Trioxide Nanoparticles

Abstract

Respiratory syncytial virus (RSV) poses a significant threat to the health of infants, children, and the elderly, and as of now there is a lack of effective therapeutic drugs. To tackle this challenge, chiral vanadium trioxide nanoparticles (V₂O₃ NPs) with a particle size of 2.56 ± 0.34 nm are successfully synthesized, exhibiting a g-factor value of 0.048 at 874 nm in terms of circular dichroism. Under 808 nm light irradiation, these chiral V₂O₃ NPs demonstrated selective cleavage of the RSV pre-fusion protein (RSV protein), effectively blocking its conformational rearrangement and preventing RSV infection both in vitro and in vivo. Experimental analysis revealed that the chiral V₂O₃ NPs specifically bind to the functional domain spanning from aspartate₂₀₀ (D₂₀₀) to asparagine₂₀₈ (N₂₀₈) in the primary sequence of the RSV protein. Notably, L-V₂O₃ NPs exhibited a higher affinity, which is 4.06 times that of D-V₂O₃ NPs and 13.55 times that of DL-V₂O₃ NPs. The precise cutting site is located between amino acid residues leucine₂₀₄ (L₂₀₄) and proline₂₀₅ (P₂₀₅), attributed to the reactive oxygen species (ROS) generated by photoinduced nanoparticles. In addition, L-V₂O₃ NPs inhibited RSV infection by 99.6% in nasal epithelial cells and 99.2% in Vero cells. In the RSV-infected mouse model, intranasal administration of L-V₂O₃ NPs effectively controlled the viral load in the lungs of mice, reducing it by 92.43%. The hematoxylin and eosin staining of mouse organs and serum biochemical indicators are similar to those of the wild-type group, indicating the biosafety of L-V₂O₃ NPs. The findings suggest that chiral nanoparticles hold great potential in controlling RSV and provide new directions and ideas for drug development against viruses.