Supramolecules for Pathogen Inhibition: From Polymers to Self-Assembled Nanosystems

Area of Science:

• Supramolecular Chemistry
• Nanotechnology
• Virology
• Materials Science

Background:

• Traditional vaccines and antivirals struggle against rapid virus mutations, as seen with COVID-19.
• Preventing virus-host cell binding is a key strategy, explored using multivalent polymers.
• Existing polymeric inhibitors often lack broad-spectrum efficacy due to viral protein diversity and rapid evolution.

Purpose of the Study:

• To develop and investigate a new class of virus inhibitors based on self-assembled supramolecular nanosystems.
• To address the limitations of current antiviral strategies by creating adaptable, broad-spectrum agents.
• To explore the potential of these nanosystems against viruses with diverse receptors and rapidly mutating spike proteins.

Main Methods:

• Engineered supramolecular nanosystems via noncovalent conjugation of small molecules/oligomers.
• Functionalized nanostructures with mucin-inspired binding groups targeting virus spike proteins.
• Utilized dynamic self-assembly for adaptive binding to multiple viral domains, accommodating mutations.

Main Results:

• Demonstrated broad-spectrum antiviral activity against herpes simplex virus (HSV), SARS-CoV-2, and influenza A virus (IAV).
• Nanosystems showed low toxicity and prevented virus-host cell interaction through binding and steric shielding.
• The dynamic nature of supramolecular assemblies allowed adaptation to mutation-driven changes in viral receptor-binding domains.

Conclusions:

• Supramolecular nanosystems represent a feasible approach for developing broad-spectrum antiviral inhibitors.
• These dynamic nanostructures offer adaptability to viral evolution, overcoming limitations of static inhibitors.
• Further research into stability, biosafety, and bioactivity is needed for clinical translation.