Exploiting protein-glycan interactions to design precision nanoparticles to inhibit viral infections: A review

Abstract

Viral infections are alarmingly rising, and some viral infections have pandemic potential. One major limitation of current treatment strategies is their inability to inhibit various viral infections and the availability of vaccines. The glycoproteins involved in virus-host interactions such as heparan sulfate proteoglycans, Dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN/R), Mannose binding lectin etc. are key to design precision nanoparticles. The glycans involved in binding to these glycan-binding proteins are polymeric mannose/fucose/sialic acid etc. The efficient interaction between these glycans and glycoproteins in host cells is dictated by ligand density, distribution, inter-glycan distance, etc. To design nanoparticle-glycan mimics that can competitively bind to viruses and deactivate them, the surface of the nanoparticles are functionalized with synthetic polymers like polyethylene glycol to make them biocompatible, and 11-mercapto-undecane sulfonate, Poly(styrene sulfonate), Mono/di mannose, Sialic acid etc. The synthesis and ligand exchange chemistry is exploited to design precision nanoparticles with defined ligand density, inter-ligand distance etc. that can spatially match the host glycoproteins thereby bind with very high affinity. This review focuses on glycoproteins involved in virus glycan recognition, common mechanism of viral infection that could be exploited to design precision nanoparticles using various ligands, limitations, and future scope.