Glycosylated Carbon Nanodots as Multivalent Blockers of Lectin-Driven Viral Entry: Structural Insights and Antiviral Performance

Abstract

A versatile nanoplatform of glycosilated carbon nanodots (glyco-CNDs) has been developed using combined pre- and post-synthetic strategies. By combining one-pot synthesis and click-chemistry functionalization, three classes of glyco-CNDs displaying distinct surface architectures and multivalent glycan presentations have been prepared. Due to the involvement of DC-SIGN and L-SIGN in SARS-CoV-2 spread through spike glycoprotein interactions, these nanostructures have further been investigated for antiviral applications. Glyco-CNDs demonstrated strong binding to DC-SIGN and achieved over 98% inhibition of trans-infection at 10 µg/mL. Confocal microscopy revealed a receptor-associated uptake pathway for one nanodot class, correlating structural features with biological performance. Importantly, glycan density alone does not dictate antiviral potency; rather, surface accessibility at the nanoscale plays a decisive role. These findings establish glyco-CNDs as a tunable and highly versatile nanoplatform for targeting lectin-mediated viral entry and highlight their potential for the development of advanced broad-spectrum antiviral materials.