title: The agmatine-containing poly(amidoamine) polymer AGMA1 binds cell surface heparan sulfates and prevents attachment of mucosal human papillomaviruses.
abstract: The agmatine-containing poly(amidoamine) polymer AGMA1 was recently shown to inhibit the infectivity of several viruses, including human papillomavirus 16 (HPV-16), that exploit cell surface heparan sulfate proteoglycans (HSPGs) as attachment receptors. The aim of this work was to assess the antiviral activity of AGMA1 and its spectrum of activity against a panel of low-risk and high-risk HPVs and to elucidate its mechanism of action. AGMA1 was found to be a potent inhibitor of mucosal HPV types (i.e., types 16, 31, 45, and 6) in pseudovirus-based neutralization assays. The 50% inhibitory concentration was between 0.34 μg/ml and 0.73 μg/ml, and no evidence of cytotoxicity was observed. AGMA1 interacted with immobilized heparin and with cellular heparan sulfates, exerting its antiviral action by preventing virus attachment to the cell surface. The findings from this study indicate that AGMA1 is a leading candidate compound for further development as an active ingredient of a topical microbicide against HPV and other sexually transmitted viral infections.
authors.affiliation: Department of Clinical and Biological Sciences, Università degli Studi di Torino, Orbassano, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Cagno
authors.affiliation: Department of Clinical and Biological Sciences, Università degli Studi di Torino, Orbassano, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Donalisio
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Bugatti
authors.affiliation: Department of Clinical and Biological Sciences, Università degli Studi di Torino, Orbassano, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Civra
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Turin, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Cavalli
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Milan, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ranucci
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ferruti
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Rusnati
authors.affiliation: Department of Clinical and Biological Sciences, Università degli Studi di Torino, Orbassano, Italy david.lembo@unito.it.
authors.forename: David
authors.initials: D
authors.lastname: Lembo
mesh_terms: D000376:Agmatine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000998:Antiviral Agents / Q000378:metabolism* / Q000494:pharmacology*; D002460:Cell Line; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D027383:Papillomaviridae / Q000187:drug effects*; D011073:Polyamines / Q000378:metabolism* / Q000494:pharmacology*; D053585:Virus Attachment / Q000187:drug effects
chemical_list: D000376:Agmatine; D000998:Antiviral Agents; D006497:Heparan Sulfate; D011073:Polyamines; C521880:AGMA1 polymer