Size-Dependent Neutralization Efficacy of Nanodecoys Against SARS-CoV-2 Mimics in Mammalian Cell Infection Models

Nanodecoys that competitively inhibit viral entry represent a promising antiviral strategy, yet the influence of their physical properties on performance remains underexplored. In this work, we systematically investigate the size-dependent antiviral activity of ACE2-conjugated nanodecoys against a safe SARS-CoV-2 mimic. Our results demonstrate that the inhibition of mimic cellular uptake is highly size-dependent. The 10 nm nanodecoys exhibited the most potent neutralization, followed by the comparable 5 and 20 nm, while the 50 and 100 nm nanodecoys demonstrated similar, lower efficacies. This work identifies nanodecoy size as a critical design principle, providing a rational framework for engineering high-performance antiviral nanotherapeutics to combat SARS-CoV-2 and other viral pathogens.