title: Soluble coxsackie- and adenovirus receptor (sCAR-Fc); a highly efficient compound against laboratory and clinical strains of coxsackie-B-virus.
abstract: Coxsackie-B-viruses (CVB) cause a wide variety of diseases, ranging from mild syndromes to life-threatening conditions such as pancreatitis, myocarditis, meningitis and encephalitis. Especially newborns and young infants develop severe diseases and long-term sequelae may occur among survivors. Due to lack of specific antiviral therapy the current treatment of CVB infection is limited to symptomatic treatment. Here we analyzed the antiviral activity of a soluble receptor fusion protein, containing the extracellular part of the coxsackievirus and adenovirus receptor (CAR) fused to the constant domain of the human IgG - sCAR-Fc - against laboratory and clinical CVB strains. We found a high overall antiviral activity of sCAR-Fc against various prototypic laboratory strains of CVB, with an inhibition of viral replication up to 3 orders of magnitude (99.9%) at a concentration of 2.5 μg/ml. These include isolates that are not dependent on CAR for infection and isolates that are resistant against pleconaril, the currently most promising anti-CVB therapeutic. A complete inhibition was observed using higher concentration of sCAR-Fc. Further analysis of 23 clinical CVB isolates revealed overall high antiviral efficiency (up to 99.99%) of sCAR-Fc. In accordance with previous data, our results confirm the strong antiviral activity of sCAR-Fc against laboratory CVB strains and demonstrate for the first time that sCAR-Fc is also highly efficient at neutralizing clinical CVB isolates. Importantly, during the sCAR-Fc inhibition experiments, no naturally occurring resistant mutants were observed.
authors: Department of Applied Biochemistry, Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany. Electronic address: sandra.pinkert@tu-berlin.de.
authors: Sandra
authors: S
authors: Pinkert
authors: Department of Applied Biochemistry, Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany.
authors: Babette
authors: B
authors: Dieringer
authors: National Reference Centre for Poliomyelitis and Enteroviruses, Robert Koch Institute, Berlin, Germany.
authors: Sabine
authors: S
authors: Diedrich
authors: IQVD - Institut für Qualitätssicherung in der Virusdiagnostik, Berlin, Germany.
authors: Heinz
authors: H
authors: Zeichhardt
authors: Department of Applied Biochemistry, Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany.
authors: Jens
authors: J
authors: Kurreck
authors: Department of Applied Biochemistry, Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany.
authors: Henry
authors: H
authors: Fechner
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D003384:Coxsackievirus Infections / Q000188:drug therapy / Q000821:virology; D029822:Enterovirus B, Human / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics* / Q000494:pharmacology; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000494:pharmacology; D012995:Solubility; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D007074:Immunoglobulin G; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins
keywords: Antiviral therapy; Clinical isolates; Coxsackievirus; Soluble receptor