Constructing safe and highly potent antiviral neutralising nanodevices using a ferritin-based plug-and-play molecular assembly platform
Abstract
Viral infections are a global threat. Vaccines and antiviral drugs take years to develop, and few options exist for rapid response to viral outbreaks. To address this gap in pandemic preparedness, we advance a “plug-and-play” nanocage assembly platform for constructing antiviral nanodevices (AVNs), defined as nanocages that physically bind viral surface glycoproteins and block entry and infection. Using a multidisciplinary approach combining molecular dynamics (MD) simulations, biochemical assays, Cryo-EM structural analysis, and antiviral assays, we show that different antiviral lectins can be genetically fused to assembly precursors designed by linking two ferritin subunits with an intrinsically disordered peptide (IDP) containing an enterokinase cleavage site. The resulting precursors significantly improved (>2-fold) lectin binding to glycans and assembled into AVNs with a core structure resembling a ferritin nanocage. We show that AVNs have potent activity against influenza A virus (IAV) (IC50 values < 1 nM), with no toxicity observed in ex vivo precision-cut lung slices (PCLS). Our data revealed insight into precursor design rules and suggest a stepwise mechanism of nanocage assembly. These findings pave the way for using AVNs to develop novel antiviral preventive strategies and provide fundamental insights into nanocage assembly.
Related
- Investigating Ferritin Permeability to Metal-Based Drugs through Molecular Dynamics
- In silico characterization of ferritin 2 conserved motifs and B-cell epitopes in Hyalomma anatolicum.
- Protocol for constructing barcoded Saccharomyces cerevisiae strains and performing pooled mating experiments
- AptViralDB: A repository of experimentally validated antiviral aptamers
- Thymoquinone and Its Nanoformulation for Dual Antiviral Therapy: Targeting Intracellular Viral Replication and Host Complications
BibTeX
@misc{sheng2026constructing,
title = {{Constructing safe and highly potent antiviral neutralising nanodevices using a ferritin-based plug-and-play molecular assembly platform}},
author = {Yujie Sheng and Yasmin M. Surani and Alina Jansen and Mickaël V. Cherrier and Lydie Martin and Elcin Su Karavelioglu and Isobel A. Manterfield and Tam T. T. Bui and Meritxell Wu-Lu and Julia A. Tree and Sally Yunsum Kim and Maria Andrea Mroginski and J. Mark Sutton and Yvain Nicolet and Kourosh H. Ebrahimi and G. Schoehn and KOUROSH Ebrahimi},
howpublished = {ChemRxiv},
year = {2026},
month = sep,
doi = {10.26434/chemrxiv.15008962/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008962/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Constructing safe and highly potent antiviral neutralising nanodevices using a ferritin-based plug-and-play molecular assembly platform
AU - Yujie Sheng
AU - Yasmin M. Surani
AU - Alina Jansen
AU - Mickaël V. Cherrier
AU - Lydie Martin
AU - Elcin Su Karavelioglu
AU - Isobel A. Manterfield
AU - Tam T. T. Bui
AU - Meritxell Wu-Lu
AU - Julia A. Tree
AU - Sally Yunsum Kim
AU - Maria Andrea Mroginski
AU - J. Mark Sutton
AU - Yvain Nicolet
AU - Kourosh H. Ebrahimi
AU - G. Schoehn
AU - KOUROSH Ebrahimi
PY - 2026
DA - 2026/09/16
PB - ChemRxiv
DO - 10.26434/chemrxiv.15008962/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008962/v1
AB - Viral infections are a global threat. Vaccines and antiviral drugs take years to develop, and few options exist for rapid response to viral outbreaks. To address this gap in pandemic preparedness, we advance a “plug-and-play” nanocage assembly platform for constructing antiviral nanodevices (AVNs), defined as nanocages that physically bind viral surface glycoproteins and block entry and infection. Using a multidisciplinary approach combining molecular dynamics (MD) simulations, biochemical assays, Cryo-EM structural analysis, and antiviral assays, we show that different antiviral lectins can be genetically fused to assembly precursors designed by linking two ferritin subunits with an intrinsically disordered peptide (IDP) containing an enterokinase cleavage site. The resulting precursors significantly improved (>2-fold) lectin binding to glycans and assembled into AVNs with a core structure resembling a ferritin nanocage. We show that AVNs have potent activity against influenza A virus (IAV) (IC50 values < 1 nM), with no toxicity observed in ex vivo precision-cut lung slices (PCLS). Our data revealed insight into precursor design rules and suggest a stepwise mechanism of nanocage assembly. These findings pave the way for using AVNs to develop novel antiviral preventive strategies and provide fundamental insights into nanocage assembly.
ER -