Multivalent Flexible Nanogels Exhibit Broad-Spectrum Antiviral Activity by Blocking Virus Entry

Area of Science:

• Biotechnology
• Virology
• Materials Science

Background:

• Viral entry into host cells relies on multivalent interactions with cell surface receptors.
• Heparan sulfate (HS) proteoglycans are initial attachment sites for many viruses, triggering subsequent entry.
• Developing antiviral agents that block these initial interactions is a key research area.

Purpose of the Study:

• To design and synthesize flexible nanogels mimicking cellular HS.
• To evaluate the nanogels' potential as broad-spectrum antiviral agents.
• To investigate the mechanism of virus-nanogel interaction and nanogel cellular uptake.

Main Methods:

• Dendritic polyglycerol sulfate-based nanogels with varying flexibility were synthesized.
• Nanogels were tested for their ability to block viral attachment and infection.
• Confocal microscopy was used to visualize virus-nanogel interactions and cellular uptake via clathrin-mediated endocytosis.

Main Results:

• The designed nanogels are nontoxic and exhibit broad-spectrum antiviral activity.
• Nanogels effectively bind to viral glycoproteins, shield virus surfaces, and block infection.
• Nanogel uptake by cells occurs through clathrin-mediated endocytosis.

Conclusions:

• Flexible nanogels mimicking HS are effective broad-spectrum antiviral agents.
• These nanogels can prevent virus entry by blocking initial HS-mediated attachment.
• The developed nanogels represent a robust strategy for inhibiting HS-dependent viral infections.