Structurally precise biohybrid nanomaterials were created by grafting various polymers to DNA with high conversions under ambient conditions. They are patterned onto DNA origami nanostructures to form customizable surface contours.

Viral infections pose a significant threat to human health and effective antiviral strategies are urgently needed. Antiviral peptides have emerged as a promising class of therapeutic agents due to their unique properties and mechanisms of action. While effective on their own, combining antiviral peptides may allow to enhance antiviral activity, broaden the antiviral spectrum, and prevent viral resistance. Here, we developed an orthogonal chemical strategy to prepare a heterodimeric peptide conjugate assembled on a protein-based nanoplatform. Specifically, we combined optimized version of two peptides inhibiting HIV-1 by distinct mechanisms. Virus-inhibitory peptide (VIRIP) is a 20 amino acid fragment of α1-antitrypsin that inhibits HIV-1 by targeting the gp41 fusion peptide. Endogenous Peptide Inhibitor of CXCR4 (EPI-X4) is a 16-residue fragment of human serum albumin that prevents HIV-1 entry by binding to the viral CXCR4 coreceptor. We assembled supramolecular nanoplatforms carrying biotinylated optimized forms of both peptides. We show that the tetravalent, bispecific assemblies show increased activity against CXCR4-tropic HIV-1variants. Our results are proof-of-concept that antiviral peptides with different modes of action can be assembled on nanoplatforms without loss of activity.

The combination of DNA-origami and synthetic polymers paves the way to a new class of structurally precise biohybrid nanomaterials for diverse applications. Herein, we introduce the grafting to method with high conversions (70-90%) under ambient conditions to generate DNA-polymer conjugates, which can hybridized precisely to DNA-origami architectures. We generated homo and block copolymers from three different polymer families (acrylates, methacrylates and acrylamides), coupled them to single stranded DNA (ssDNA) and pattern different DNA-origami architectures to demonstrate the formation of precise surface nanopatterns.