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

African swine fever virus (ASFV) is one of the most dangerous viruses for pigs and is endemic in Africa but recently also spread into the Russian Federation and the Eastern border of the EU. So far there is no vaccine or antiviral drug available to curtail the infection. Thus, control strategies based on novel inhibitors are urgently needed. Another highly relevant virus infection in pigs is Aujeszky's disease caused by the alphaherpesvirus pseudorabies virus (PrV). This article reports the synthesis and biological evaluation of novel extracellular matrix-inspired entry inhibitors based on polyglycerol sulfate-functionalized graphene sheets. The developed 2D architectures bind enveloped viruses during the adhesion process and thereby exhibit strong inhibitory effects, which are equal or better than the common standards enrofloxacin and heparin as demonstrated for ASFV and PrV. Overall, the developed polyvalent 2D entry inhibitors are nontoxic and efficient nanoarchitectures, which interact with various types of enveloped viruses. Therefore they prevent viral adhesion to the host cell and especially target viruses that rely on a heparan sulfate-dependent cell entry mechanism.

Controlled Covalent Functionalization of Thermally Reduced Graphene Oxide To Generate Defined Bifunctional 2D Nanomaterials.

A controlled, reproducible, gram-scale method is reported for the covalent functionalization of graphene sheets by a one-pot nitrene [2+1] cycloaddition reaction under mild conditions. The reaction between commercially available 2,4,6-trichloro-1,3,5-triazine and sodium azide with thermally reduced graphene oxide (TRGO) results in defined dichlorotriazine-functionalized sheets. The different reactivities of the chlorine substituents on the functionalized graphene allow stepwise post-modification by manipulating the temperature. This new method provides unique access to defined bifunctional 2D nanomaterials, as exemplified by chiral surfaces and multifunctional hybrid architectures.

Highly Efficient Multivalent 2D Nanosystems for Inhibition of Orthopoxvirus Particles.

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.

Multivalency at Interfaces: Supramolecular Carbohydrate-Functionalized Graphene Derivatives for Bacterial Capture, Release, and Disinfection.

A supramolecular carbohydrate-functionalized two-dimensional (2D) surface was designed and synthesized by decorating thermally reduced graphene sheets with multivalent sugar ligands. The formation of host-guest inclusions on the carbon surface provides a versatile strategy, not only to increase the intrinsic water solubility of graphene-based materials, but more importantly to let the desired biofunctional binding groups bind to the surface. Combining the vital recognition role of carbohydrates and the unique 2D large flexible surface area of the graphene sheets, the addition of multivalent sugar ligands makes the resulting carbon material an excellent platform for selectively wrapping and agglutinating Escherichia coli (E. coli). By taking advantage of the responsive property of supramolecular interactions, the captured bacteria can then be partially released by adding a competitive guest. Compared to previously reported scaffolds, the unique thermal IR-absorption properties of graphene derivatives provide a facile method to kill the captured bacteria by IR-laser irradiation of the captured graphene-sugar-E. coli complex.

Carbon-based cores with polyglycerol shells - the importance of core flexibility for encapsulation of hydrophobic guests.

Two core-shell nanoparticles with polyglycerol shells and sp3 carbon cores with different flexibilities (soft dendritic polyethylene and hard nanodiamond) were synthesized, their encapsulation capacities were compared, and their ability to transport into tumor cells was investigated. The nanocarrier with a soft core was superior to the hard one.