LAUSR

Significance The Achilles heel of the best available antiviral mRNA vaccines and biomolecular drugs includes the loss of their potency due to viral mutations and thermal exposure. Chiral L- or D-penicillamine-coated CuS nanoparticles (NPs) provide an additional pathway to address these problems. The geometric complementary of their twisted conical shape to the spike protein of SARS-CoV-2 results in agglutination of the virus with antibody-like efficiency. Strong nanoparticle–protein interactions lead to broad-spectrum antiviral activity for several SARS-CoV-2 variants. An inhalable nano-formulation effectively protected mice from SARS-CoV-2 infection for 72 h. The combination of temperature robustness, curative capabilities, and broad activity makes possible utilization of chiral NPs as rapid-deployment antivirals for first responders and emergency biomedical stockpiles for potential pandemics.