Bioactive Polysulfate-Based Nano-Assemblies Against Virus Infection

Area of Science:

• Nanotechnology
• Virology
• Biomaterials Science

Background:

• Polysulfated nanosystems demonstrate potent antiviral properties by dynamically deforming and adhering to viruses.
• Developing novel supramolecular nanostructures is crucial for enhancing antiviral efficacy.

Purpose of the Study:

• To present a novel supramolecular nanosystem assembled from a block copolymer for enhanced virus inhibition.
• To evaluate the antiviral efficacy of varying sulfation levels on the nanosystem against herpes simplex virus type-1 (HSV-1) and Omicron variants.

Main Methods:

• Assembly of a block copolymer into 100 nm spheres with a brush-like corona.
• Testing varying sulfation levels (45%, 76%, 100%) in plaque reduction assays for HSV-1 inhibition.
• Cryo-electron microscopy (cryo-EM) to visualize virus-nanosystem interactions.
• Evaluation in post-infection models and against Omicron variants.

Main Results:

• Nanosystems exhibited exceptional particle homogeneity due to outer-shell sulfate distribution, enhancing multivalent interactions.
• Achieved very low half-maximal inhibition concentration (IC50) values for HSV-1: 0.43, 0.16, and 0.037 µg/mL for 45%, 76%, and 100% sulfated assemblies, respectively.
• Cryo-EM confirmed multiple layers of nanosystems trapping viruses.
• 76% and 100% sulfated assemblies demonstrated therapeutic potential in post-infection models and against Omicron.

Conclusions:

• The 3D flexible nano-assemblies effectively block virus entry into host cells.
• Superior morphology and high efficiency make these sulfated nanosystems promising candidates for broad-spectrum antiviral applications.