Highly Efficient Multivalent 2D Nanosystems for Inhibition of Orthopoxvirus Particles

Abstract

Efficient inhibition of cell-pathogen interaction to prevent subsequent infection is an urgent but yet unsolved problem. In this study, the synthesis and functionalization of novel multivalent 2D carbon nanosystems as well as their antiviral efficacy in vitro are shown. For this reason, a new multivalent 2D flexible carbon architecture is developed in this study, functionalized with sulfated dendritic polyglycerol, to enable virus interaction. A simple "graft from" approach enhances the solubility of thermally reduced graphene oxide and provides a suitable 2D surface for multivalent ligand presentation. Polysulfation is used to mimic the heparan sulfate-containing surface of cells and to compete with this natural binding site of viruses. In correlation with the degree of sulfation and the grafted polymer density, the interaction efficiency of these systems can be varied. In here, orthopoxvirus strains are used as model viruses as they use heparan sulfate for cell entry as other viruses, e.g., herpes simplex virus, dengue virus, or cytomegalovirus. The characterization results of the newly designed graphene derivatives demonstrate excellent binding as well as efficient inhibition of orthopoxvirus infection. Overall, these new multivalent 2D polymer nanosystems are promising candidates to develop potent inhibitors for viruses, which possess a heparan sulfate-dependent cell entry mechanism.

Interactions of Fullerene‐Polyglycerol Sulfates at Viral and Cellular Interfaces

“…Graphene sheets with polyglycerol sulfate coverage strongly interact with herpes simplex, orthopox, and african swine flu viruses . Similar outcomes have also been found for sulfated gold nanoparticles and graphene sheets against vesicular stomatitis virus (VSV).…”

Polyvalent 2D Entry Inhibitors for Pseudorabies and African Swine Fever Virus

“…According to the method of Haag and co‐workers, TRGO–lPG (50.0 mg) was dispersed in pro analysis dimethylformamide (p.a. DMF) (11 mL) using an ultrasonic bath at 35 °C under inert conditions.…”

Multivalent Interactions between 2D Nanomaterials and Biointerfaces

“…Recently, our group developed a range of new sulfated graphene derivatives and further explored their utility for virus inhibition. Thermally reduced graphene oxide (TRGO) sheets modified with biocompatible hyperbranched polyglycerol (hPG) via a grafting‐from method and then the hydroxylic groups were sulfated to generate heparin mimic 2D nanomaterials ( Figure ) . These sulfated TRGO‐hPG sheets exhibited good binding and inhibition efficiency for orthopoxvirus and herpesvirus strains; the interactions could be tuned by varying the sulfation degree and the grafted polymer density .…”

“…Thermally reduced graphene oxide (TRGO) sheets modified with biocompatible hyperbranched polyglycerol (hPG) via a grafting‐from method and then the hydroxylic groups were sulfated to generate heparin mimic 2D nanomaterials ( Figure ) . These sulfated TRGO‐hPG sheets exhibited good binding and inhibition efficiency for orthopoxvirus and herpesvirus strains; the interactions could be tuned by varying the sulfation degree and the grafted polymer density . The impact of TRGO sheet size and degree of sulfation on their antiviral ability were subsequently investigated, and it was shown that graphene sheets with smaller sizes (≈300 nm diameter) with a 10% degree of sulfation gave the highest efficiency of virus inhibition.…”