Work

Constructing safe and highly potent antiviral neutralising nanodevices using a ferritin-based plug-and-play molecular assembly platform

Year: 2026

Type: preprint

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.

Source: ChemRxiv

DOI: 10.26434/chemrxiv.15008962/v1