Broad-Spectrum Virus Trapping with Heparan Sulfate-Modified DNA Origami Shells

Area of Science:

• Nanotechnology
• Virology
• Biochemistry

Background:

• Current antiviral strategies are often virus-specific and limited in scope.
• There is a critical need for broad-spectrum antiviral platforms effective against diverse and emerging viral pathogens.
• Viruses commonly interact with heparan sulfate proteoglycans (HSPG) on host cell surfaces.

Purpose of the Study:

• To develop a universal virus-trapping platform using DNA origami.
• To investigate the potential of HSPG-mimicking DNA nanostructures for broadband antiviral activity.
• To assess the encapsulation efficiency of various viruses and virus-like particles within these nanostructures.

Main Methods:

• Fabrication of DNA origami shells functionalized with heparin and heparan sulfate (HS) derivatives.
• Testing the encapsulation capacity of HS-functionalized shells against a panel of viruses (adeno, AAV, chikungunya, dengue, HPV, noro, polio, rubella, SARS-CoV-2).
• Evaluating the mechanism of virus trapping based on avidity and HSPG affinity.

Main Results:

• The HS-functionalized DNA origami shells demonstrated broadband virus trapping capabilities.
• A single shell system successfully encapsulated multiple types of viruses and virus-like particles without specific binders.
• Multiple virus particles could be trapped per shell, and shells could aggregate on virus clusters, providing steric hindrance.

Conclusions:

• DNA origami shells functionalized with HS derivatives offer a versatile and effective platform for broad-spectrum virus trapping.
• This approach bypasses the need for virus-specific targeting, presenting a novel strategy for antiviral interventions.
• The steric occlusion effect may prevent viral entry into host cells, suggesting potential therapeutic applications.