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 (V 2 O 3 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 V 2 O 3 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 V 2 O 3 NPs specifically bind to the functional domain spanning from aspartate 200 (D 200 ) to asparagine 208 (N 208 ) in the primary sequence of the RSV protein. Notably, L ‐V 2 O 3 NPs exhibited a higher affinity, which is 4.06 times that of D ‐V 2 O 3 NPs and 13.55 times that of DL ‐V 2 O 3 NPs. The precise cutting site is located between amino acid residues leucine 204 (L 204 ) and proline 205 (P 205 ), attributed to the reactive oxygen species (ROS) generated by photoinduced nanoparticles. In addition, L ‐V 2 O 3 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.