title: Sulfated derivatives of Escherichia coli K5 capsular polysaccharide are potent inhibitors of human cytomegalovirus.
abstract: To date, there are few drugs licensed for the treatment of human cytomegalovirus (HCMV) infections, most of which target the viral DNA polymerase and suffer from many drawbacks. Thus, there is still a strong need for new anti-HCMV compounds with novel mechanisms of action. In this study, we investigated the anti-HCMV activity of chemically sulfated derivatives of Escherichia coli K5 capsular polysaccharide. These compounds are structurally related to cellular heparan sulfate and have been previously shown to be effective against some enveloped and nonenveloped viruses. We demonstrated that two derivatives, i.e., K5-N,OS(H) and K5-N,OS(L), are able to prevent cell infection by different strains of HCMV at concentrations in the nanomolar range while having no significant cytotoxicity. Studies performed to elucidate the mechanism of action of their anti-HCMV activity revealed that these compounds do not interact with either the host cell or the viral particle but need a virus-cell interaction to exert antiviral effects. Furthermore, these K5 derivatives were able to inhibit the attachment step of HCMV infection, as well as the viral cell-to-cell spread. Since the mode of inhibition of these compounds appears to differ from that of the available anti-HCMV drugs, sulfated K5 derivatives could represent the basis for the development of a novel class of potent anti-HCMV compounds. Interestingly, our studies highlight that small variations of the K5 derivatives structure can modulate the selectivity and potency of their activities against different viruses, including viruses belonging to the same family.
authors: Department of Histology, Microbiology and Medical Biotechnologies, University of Padua, via Gabelli 63, Padua, Italy.
authors: Beatrice
authors: B
authors: Mercorelli
authors: Pasqua
authors: P
authors: Oreste
authors: Elisa
authors: E
authors: Sinigalia
authors: Giulia
authors: G
authors: Muratore
authors: David
authors: D
authors: Lembo
authors: Giorgio
authors: G
authors: Palù
authors: Arianna
authors: A
authors: Loregian
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D016667:Bacterial Capsules / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D003587:Cytomegalovirus / Q000187:drug effects*; D004926:Escherichia coli / Q000737:chemistry*; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D013431:Sulfates / Q000737:chemistry*; D014771:Virion / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D013431:Sulfates; C050673:capsular polysaccharide K5