Peptide-functionalized nanoparticles were proposed as promising inhibitors for SARS-CoV-2 proliferation, but the effective conjugation process and the dynamic multivalent binding towards a specific target need further investigation. Here, we develop the truncated ACE2 peptide-conjugated gold nanoparticles with helical propensity and vertically oriented packing to maximize the antiviral activity. The binding study demonstrate their reduction efficiency upon the interaction with SARS-CoV-2 RBD, indicating a up to 99% and a high binding affinity of 31 nM. It also shows rapid multivalent binding and the long-lasting fixation to SARS-CoV-2 RBD in an excess scenario for 12 hours, which is still specific despite the presence of other proteins. Our study implies a safe, simple, and tunable strategy to improve the efficacy of peptide inhibitors for potential clinical use and facilitate the design of antiviral agents to combat the virus variants in the future.

Truncated Angiotensin Converting Enzyme-2 Peptide-Conjugated Gold Nanoparticles as an Efficient, Specific, and Long-Lasting Antiviral Platform to Combat SARS-CoV-2

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