tetano
Editor, Senior Moderator
J Am Chem Soc
. 2024 Feb 26.
doi: 10.1021/jacs.3c11760. Online ahead of print. Polyvalent Nanobody Structure Designed for Boosting SARS-CoV-2 Inhibition
Tingjie Song[SUP] 1 2 3 [/SUP], Laura Cooper[SUP] 4 [/SUP], Jazmin Galván Achi[SUP] 4 [/SUP], Xiaojing Wang[SUP] 1 2 3 [/SUP], Abhisek Dwivedy[SUP] 1 2 5 [/SUP], Lijun Rong[SUP] 4 [/SUP], Xing Wang[SUP] 1 2 3 5 [/SUP]
Affiliations
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) assays show that the PNS binds the SARS-CoV-2 trimeric spike proteins with a ∼1000-fold improvement in affinity than that of monomeric Nbs. Furthermore, our viral entry inhibition assays using the PNS against SARS-CoV-2 WA/2020 and two recent variants of interest (BQ1.1 and XBB) show an over 400-fold enhancement in viral inhibition compared to free Nbs. Our PNS strategy built on a new DNA-protein conjugation chemistry provides a facile approach to developing robust virus inhibitors by using a corresponding virus-targeting Nb with a desired Nb density.
. 2024 Feb 26.
doi: 10.1021/jacs.3c11760. Online ahead of print. Polyvalent Nanobody Structure Designed for Boosting SARS-CoV-2 Inhibition
Tingjie Song[SUP] 1 2 3 [/SUP], Laura Cooper[SUP] 4 [/SUP], Jazmin Galván Achi[SUP] 4 [/SUP], Xiaojing Wang[SUP] 1 2 3 [/SUP], Abhisek Dwivedy[SUP] 1 2 5 [/SUP], Lijun Rong[SUP] 4 [/SUP], Xing Wang[SUP] 1 2 3 5 [/SUP]
Affiliations
- PMID: 38408177
- DOI: 10.1021/jacs.3c11760
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) assays show that the PNS binds the SARS-CoV-2 trimeric spike proteins with a ∼1000-fold improvement in affinity than that of monomeric Nbs. Furthermore, our viral entry inhibition assays using the PNS against SARS-CoV-2 WA/2020 and two recent variants of interest (BQ1.1 and XBB) show an over 400-fold enhancement in viral inhibition compared to free Nbs. Our PNS strategy built on a new DNA-protein conjugation chemistry provides a facile approach to developing robust virus inhibitors by using a corresponding virus-targeting Nb with a desired Nb density.