Nontoxic linear polyglycerol sialosides block influenza entry via multivalent hemagglutinin binding, outperforming Tamiflu in potency.

Detailed Explanation

This invention introduces linear polyglycerol compounds grafted with sialic acid derivatives at 10–100% substitution levels. The linear architecture allows fine-tuned control over ligand density, size (1–100 kDa), and spacing, leading to superior hemagglutinin inhibition compared to hyperbranched analogs. Two synthesis routes—thiol-ene and copper-catalyzed click chemistry—yield diverse linkers. In vitro assays show IC₅₀ values as low as 5.9 µM for 73% functionalization, a dramatic improvement over Tamiflu’s millimolar range. In vivo mouse models confirm significant prophylactic and therapeutic efficacy, especially when combined with neuraminidase inhibitors.

Key Innovation Features and Advantages

• Precisely tunable substitution (10–100%) for optimal multivalent binding
• Linear backbone boosts antiviral activity at low micromolar concentrations – Proven non-toxicity in cell and animal models
• Versatile click chemistry routes enable diverse functional linkers
• Demonstrated synergy with neuraminidase inhibitors

 Use Cases

• Prophylactic nasal spray for high-risk influenza exposure
• Therapeutic agent against seasonal and avian influenza
• Combined drug regimens with Tamiflu for resistance mitigation
• Exploration as antibacterial or anti-inflammatory macromolecule

Commercial Opportunities

• Licensing to pharma for novel multivalent antivirals
• Co-development of polymer–drug combination therapies
• Veterinary applications against livestock influenza outbreaks
• Platform extension to other enveloped viruses

 Current Status

Compounds synthesized, characterized, and validated in vitro and in mouse infection models. Ready for lead optimization and preclinical safety studies.