Photoactive Chiral Nanoneedles for Site-Selective Cleavage and Broad-Spectrum Inactivation of Viruses

Abstract

Abstract Respiratory viruses spread through aerosols and contaminated surfaces, yet masks, respirators, and filters only trap pathogens without inactivating them, turning used protective equipment into a secondary transmission source. Here, we report chiral ZnO nanoneedles (L-NNs or D-NNs), stabilized by L- or D-phenylalanine-penicillamine-phenylalanine (L-FPF or D-FPF), as a capture-and-kill coating that targets the heptad repeat 2 (HR2) of class I viral fusion proteins. Through chirality-matched multivalent interactions, L-NNs bind the amphipathic HR2 stem with high affinity and block the six-helix bundle (6-HB) assembly essential for membrane fusion, showing a potency (IC50 = 0.52 ng/mL) approximately 8-fold higher than that of D-NNs (IC50 = 4.11 ng/mL) and 120-fold higher than that of achiral NNs (IC50 = 66.73 ng/mL). Chiral ligands narrow the ZnO bandgap and, through chirality-induced spin selectivity that suppresses charge recombination, enable 405 nm light-driven proteolytic activity that hydrolyzes specific amide bonds between acidic and hydrophobic residues within HR2. Because photogenerated reactive species act over only nanometer distances, affinity capture immobilizes virions at the photocatalytic needle surface and converts nonspecific oxidation to spatially confined, target-directed catalysis, enabling irreversible inactivation at low light doses. Targeting the evolutionarily conserved fusion core, L-NNs exhibit broad-spectrum activity across Ebola, coronaviruses, HIV-1, and HRSV, with IC50 values below 26.88 ng/mL, and show favorable biocompatibility. This work establishes chirality-engineered nanomaterials as a precision virucidal platform for photoresponsive protective coatings that interrupt environmental transmission of diverse and emerging viruses.