title: Sulfated K5 Escherichia coli polysaccharide derivatives: A novel class of candidate antiviral microbicides.
abstract: Antiviral microbicides, topical agents that prevent sexually transmitted infections, mainly work by blocking the interaction between viral proteins and cell surface components. In many instances, virus-cell interaction is mediated by cell surface heparan sulfate proteoglycans (HSPGs). HSPGs are exploited as attachment receptors by three sexually transmitted viruses: Human Immunodeficiency Virus (HIV), Herpes Simplex Virus (HSV) and Human Papilloma Virus (HPV). Since these viruses can either infect or co-infect humans, virus/HSPGs interaction is a preferential target for the development of wide-spectrum antiviral microbicides. Several polyanionic compounds prevent HIV, HSV and HPV infections in cell culture models by acting as heparan sulfate (HS)-antagonists. However, three promising polyanionic compounds recently failed to pass phase III clinical trials designed to establish their efficacy in preventing HIV acquisition. In this scenario, new polyanionic compounds must be added to the pipeline of candidate microbicides and their development as effective drugs reconsidered. The capsular K5 polysaccharide from Escherichia coli has the same structure as the heparin/HS biosynthetic precursor. Chemical and enzymatic modifications have led to the synthesis of K5 derivatives with different degrees of sulfation and charge distribution and devoid of anticoagulant activity and cell toxicity. Recently attracting attention as candidate microbicides, they potently inhibit a broad spectrum of HIV-1 strains and genital types of HPV and HSV-1 and 2 in vitro. With a focus on the K5 derivatives, this article reviews the literature on polyanions as antiviral microbicides and discusses the possible therapeutic implications of this novel class of compounds.
authors.affiliation: Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia, 25123 Brescia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Rusnati
authors.forename: Elisa
authors.initials: E
authors.lastname: Vicenzi
authors.forename: Manuela
authors.initials: M
authors.lastname: Donalisio
authors.forename: Pasqua
authors.initials: P
authors.lastname: Oreste
authors.forename: Santo
authors.initials: S
authors.lastname: Landolfo
authors.forename: David
authors.initials: D
authors.lastname: Lembo
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D016667:Bacterial Capsules / Q000737:chemistry / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D004926:Escherichia coli / Q000737:chemistry*; D015658:HIV Infections / Q000188:drug therapy / Q000503:physiopathology; D006561:Herpes Simplex / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D030361:Papillomavirus Infections / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D000998:Antiviral Agents; C050673:capsular polysaccharide K5