biostudies-literatureSong TNational Institute of Allergy and Infectious DiseasesNIAID NIH HHS5894-5900https://www.ebi.ac.uk/biostudies/studies/S-EPMC10965196biostudies-literatureUnknown146(9)Coronavirus transmission and mutations have brought intensive challenges on pandemic control and disease treatment. Developing robust and versatile antiviral drugs for viral neutralization is highly desired. Here, we created a new polyvalent nanobody (Nb) structure that shows the effective inhibition of SARS-CoV-2 infections. Our polyvalent Nb structure, called "PNS", is achieved by first conjugating single-stranded DNA (ssDNA) and the receptor-binding domain (RBD)-targeting Nb with retained binding ability to SARS-CoV-2 spike protein and then coalescing the ssDNA-Nb conjugates around a gold nanoparticle (AuNP) via DNA hybridization with a desired Nb density that offers spatial pattern-matching with that of the Nb binding sites on the trimeric spike. The surface plasmon resonance (SPR) assJournal of the American Chemical SocietyPolyvalent Nanobody Structure Designed for Boosting SARS-CoV-2 Inhibition.PMC10965196R01 AI159454R21AI166898R21 AI166898R01AI159454Cooper LSong TDwivedy AWang XGalvan Achi JRong LfalsePolyvalent Nanobody Structure Designed for Boosting SARS-CoV-2 Inhibition.Coronavirus transmission and mutations have brought intensive challenges on pandemic control and disease treatment. Developing robust and versatile antiviral drugs for viral neutralization is highly desired. Here, we created a new polyvalent nanobody (Nb) structure that shows the effective inhibition of SARS-CoV-2 infections. Our polyvalent Nb structure, called "PNS", is achieved by first conjugating single-stranded DNA (ssDNA) and the receptor-binding domain (RBD)-targeting Nb with retained binding ability to SARS-CoV-2 spike protein and then coalescing the ssDNA-Nb conjugates around a gold nanoparticle (AuNP) via DNA hybridization with a desired Nb density that offers spatial pattern-matching with that of the Nb binding sites on the trimeric spike. The surface plasmon resonance (SPR) ass2024-01-01T00:00:00Z2024 Mar2025-04-18T21:20:25.45Z2025-04-07T09:17:08.602ZS-EPMC109651963840817710.1021/jacs.3c11760