title: Polyvalent 2D Entry Inhibitors for Pseudorabies and African Swine Fever Virus.
abstract: 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.
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität, 14195, Berlin, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ziem
authors.affiliation: Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493, Greifswald-Insel Riems, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Rahn
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität, 14195, Berlin, Germany.
authors.forename: Ievgen
authors.initials: I
authors.lastname: Donskyi
authors.affiliation: Institute of Laboratory Medicine, Charité-Universitätsmedizin Berlin, 13353, Berlin, Germany.
authors.forename: Kim
authors.initials: K
authors.lastname: Silberreis
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität, 14195, Berlin, Germany.
authors.forename: Luis
authors.initials: L
authors.lastname: Cuellar
authors.affiliation: Institute of Laboratory Medicine, Charité-Universitätsmedizin Berlin, 13353, Berlin, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Dernedde
authors.affiliation: Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493, Greifswald-Insel Riems, Germany.
authors.forename: Günther
authors.initials: G
authors.lastname: Keil
authors.affiliation: Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493, Greifswald-Insel Riems, Germany.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Mettenleiter
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität, 14195, Berlin, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Haag
mesh_terms: D000357:African Swine Fever / Q000188:drug therapy* / Q000821:virology; D000358:African Swine Fever Virus / Q000187:drug effects / Q000472:pathogenicity; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000627:therapeutic use*; D005990:Glycerol / Q000737:chemistry / Q000627:therapeutic use; D006108:Graphite / Q000737:chemistry / Q000627:therapeutic use; D011558:Herpesvirus 1, Suid / Q000187:drug effects / Q000472:pathogenicity; D006801:Humans; D011108:Polymers / Q000737:chemistry / Q000627:therapeutic use; D011557:Pseudorabies / Q000188:drug therapy* / Q000821:virology; D013552:Swine; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D011108:Polymers; C043941:polyglycerol; D006108:Graphite; D005990:Glycerol
keywords: African swine fever virus; polyglycerol sulfate; pseudorabies virus; thermally reduced graphene oxide; virus entry inhibitor