title: 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.
authors: Institute of Chemistry and Biochemistry, Freie Universität, 14195, Berlin, Germany.
authors: Benjamin
authors: B
authors: Ziem
authors: Institute of Virology, University of Leipzig, 04103, Leipzig, Germany.|Robert Koch Institute, Center for Biological Threats and Special Pathogens, 13353, Berlin, Germany.
authors: Hendrik
authors: H
authors: Thien
authors: Institute of Chemistry and Biochemistry, Freie Universität, 14195, Berlin, Germany.
authors: Katharina
authors: K
authors: Achazi
authors: Robert Koch Institute, Center for Biological Threats and Special Pathogens, 13353, Berlin, Germany.
authors: Constanze
authors: C
authors: Yue
authors: Robert Koch Institute, Center for Biological Threats and Special Pathogens, 13353, Berlin, Germany.
authors: Daniel
authors: D
authors: Stern
authors: Robert Koch Institute, Center for Biological Threats and Special Pathogens, 13353, Berlin, Germany.
authors: Kim
authors: K
authors: Silberreis
authors: Institute for Physics and IRIS Adlershof, Humboldt-Universität Berlin, 12489, Berlin, Germany.
authors: Mohammad Fardin
authors: MF
authors: Gholami
authors: Institute for Macromolecular Chemistry, University of Freiburg, 79104, Freiburg, Germany.
authors: Fabian
authors: F
authors: Beckert
authors: Institute of Chemistry and Biochemistry, Freie Universität, 14195, Berlin, Germany.
authors: Dominic
authors: D
authors: Gröger
authors: Institute for Macromolecular Chemistry, University of Freiburg, 79104, Freiburg, Germany.
authors: Rolf
authors: R
authors: Mülhaupt
authors: Institute for Physics and IRIS Adlershof, Humboldt-Universität Berlin, 12489, Berlin, Germany.
authors: Jürgen P
authors: JP
authors: Rabe
authors: Robert Koch Institute, Center for Biological Threats and Special Pathogens, 13353, Berlin, Germany.
authors: Andreas
authors: A
authors: Nitsche
authors: Institute of Chemistry and Biochemistry, Freie Universität, 14195, Berlin, Germany.
authors: Rainer
authors: R
authors: Haag
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000737:chemistry*; D002244:Carbon / Q000008:administration & dosage / Q000737:chemistry; D005990:Glycerol / Q000008:administration & dosage / Q000737:chemistry; D006108:Graphite / Q000008:administration & dosage / Q000737:chemistry; D006497:Heparan Sulfate / Q000008:administration & dosage / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D018155:Orthopoxvirus / Q000187:drug effects*; D010087:Oxides / Q000008:administration & dosage / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry; D013552:Swine
chemical_list: D000998:Antiviral Agents; D002244:Carbon; D005990:Glycerol; D006108:Graphite; D006497:Heparan Sulfate; D010087:Oxides; D011108:Polymers; C043941:polyglycerol
keywords: dendritic polyglycerol sulfate; heparin analogue; orthopoxvirus; thermally reduced graphene oxide; virus inhibitors