title: Basic chemokine-derived glycosaminoglycan binding peptides exert antiviral properties against dengue virus serotype 2, herpes simplex virus-1 and respiratory syncytial virus.
abstract: Chemokines attract leukocytes to sites of infection in a G protein-coupled receptor (GPCR) and glycosaminoglycan (GAG) dependent manner. Therefore, chemokines are crucial molecules for proper functioning of our antimicrobial defense mechanisms. In addition, some chemokines have GPCR-independent defensin-like antimicrobial activities against bacteria and fungi. Recently, high affinity for GAGs has been reported for the positively charged COOH-terminal region of the chemokine CXCL9. In addition to CXCL9, also CXCL12γ has such a positively charged COOH-terminal region with about 50% positively charged amino acids. In this report, we compared the affinity of COOH-terminal peptides of CXCL9 and CXCL12γ for GAGs and KD values in the low nM range were detected. Several enveloped viruses such as herpesviruses, hepatitis viruses, human immunodeficiency virus (HIV), dengue virus (DENV), etc. are known to bind to GAGs such as the negatively charged heparan sulfate (HS). In this way GAGs are important for the initial contacts between viruses and host cells and for the infection of the cell. Thus, inhibiting the virus-cell interactions, by blocking GAG-binding sites on the host cell, might be a way to target multiple virus families and resistant strains. This article reports that the COOH-terminal peptides of CXCL9 and CXCL12γ have antiviral activity against DENV serotype 2, clinical and laboratory strains of herpes simplex virus (HSV)-1 and respiratory syncytial virus (RSV). Moreover, we show that CXCL9(74-103) competes with DENV envelope protein domain III for binding to heparin. These short chemokine-derived peptides may be lead molecules for the development of novel antiviral agents.
authors.affiliation: KU Leuven, University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Immunology, B-3000 Leuven, Belgium. Electronic address: vincent.vanheule@rega.kuleuven.be.
authors.forename: Vincent
authors.initials: V
authors.lastname: Vanheule
authors.affiliation: KU Leuven, University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium. Electronic address: peter.vervaeke@rega.kuleuven.be.
authors.forename: Peter
authors.initials: P
authors.lastname: Vervaeke
authors.affiliation: KU Leuven, University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Immunology, B-3000 Leuven, Belgium. Electronic address: anneleen.mortier@rega.kuleuven.be.
authors.forename: Anneleen
authors.initials: A
authors.lastname: Mortier
authors.affiliation: KU Leuven, University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium. Electronic address: sam.noppen@rega.kuleuven.be.
authors.forename: Sam
authors.initials: S
authors.lastname: Noppen
authors.affiliation: KU Leuven, University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Immunology, B-3000 Leuven, Belgium. Electronic address: mieke.gouwy@rega.kuleuven.be.
authors.forename: Mieke
authors.initials: M
authors.lastname: Gouwy
authors.affiliation: KU Leuven, University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium. Electronic address: robert.snoeck@rega.kuleuven.be.
authors.forename: Robert
authors.initials: R
authors.lastname: Snoeck
authors.affiliation: KU Leuven, University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium. Electronic address: graciela.andrei@rega.kuleuven.be.
authors.forename: Graciela
authors.initials: G
authors.lastname: Andrei
authors.affiliation: KU Leuven, University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Immunology, B-3000 Leuven, Belgium. Electronic address: jo.vandamme@rega.kuleuven.be.
authors.forename: Jo
authors.initials: J
authors.lastname: Van Damme
authors.affiliation: KU Leuven, University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium. Electronic address: sandra.liekens@rega.kuleuven.be.
authors.forename: Sandra
authors.initials: S
authors.lastname: Liekens
authors.affiliation: KU Leuven, University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Immunology, B-3000 Leuven, Belgium. Electronic address: paul.proost@rega.kuleuven.be.
authors.forename: Paul
authors.initials: P
authors.lastname: Proost
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism* / Q000494:pharmacology; D016466:CHO Cells; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D054370:Chemokine CXCL9 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D018925:Chemokines / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D003716:Dengue Virus / Q000187:drug effects / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism* / Q000494:pharmacology; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D012136:Respiratory Syncytial Viruses / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; C515255:CXCL12 protein, human; C080810:CXCL9 protein, human; D054377:Chemokine CXCL12; D054370:Chemokine CXCL9; D018925:Chemokines; D006025:Glycosaminoglycans
keywords: Antiviral activity; Chemokine; Dengue virus; Glycosaminoglycan; Heparan sulfate