Sulfonated and Carboxymethylated β-Glucan Derivatives with Inhibitory Activity against Herpes and Dengue Viruses

International Journal of Molecular Sciences

Robert F. H. Dekker¹  Mário A. A. Cunha²  Václav Vetvicka³  Alexandre Orsato⁴  Vinicius Seiki Takemura Quinteiro⁴  José Louzinho Lopes⁴  Aneli M. Barbosa-Dekker⁴  Maria Laura Darido⁵  Jéssica Wouk⁵  Ligia Carla Faccin-Galhardi⁵ 

[1] Beta-Glucan Produtos Farmoquímicos EIRELI, Lote 24A, Bloco Zircônia, Universidade Tecnológica Federal do Paraná, Câmpus Londrina, Londrina CEP 86036-700, Parana, Brazil;Department of Chemistry, Universidade Tecnológica Federal do Paraná, Pato Branco CEP 85503-390, Parana, Brazil;Department of Pathology and Laboratory Medicine, University of Louisville, Louisville, KY 40292, USA;Laboratory of Synthesis of Medicinal Molecules (LaSMMed), Department of Chemistry, CCE, Universidade Estadual de Londrina, Londrina CEP 86057-970, Parana, Brazil;Laboratory of Virology, Department of Microbiology, CCB, Universidade Estadual de Londrina, Londrina CEP 86057-970, Parana, Brazil;

关键词: (1→3)(1→6)-β-D-glucan;    antivirals;    anionic polysaccharides;    herpes simplex virus;    dengue virus;   

DOI  :  10.3390/ijms222011013

来源: DOAJ

【 摘 要 】

The infection of mammalian cells by enveloped viruses is triggered by the interaction of viral envelope glycoproteins with the glycosaminoglycan, heparan sulfate. By mimicking this carbohydrate, some anionic polysaccharides can block this interaction and inhibit viral entry and infection. As heparan sulfate carries both carboxyl and sulfate groups, this work focused on the derivatization of a (1→3)(1→6)-β-D-glucan, botryosphaeran, with these negatively-charged groups in an attempt to improve its antiviral activity. Carboxyl and sulfonate groups were introduced by carboxymethylation and sulfonylation reactions, respectively. Three derivatives with the same degree of carboxymethylation (0.9) and different degrees of sulfonation (0.1; 0.2; 0.4) were obtained. All derivatives were chemically characterized and evaluated for their antiviral activity against herpes (HSV-1, strains KOS and AR) and dengue (DENV-2) viruses. Carboxymethylated botryosphaeran did not inhibit the viruses, while all sulfonated-carboxymethylated derivatives were able to inhibit HSV-1. DENV-2 was inhibited only by one of these derivatives with an intermediate degree of sulfonation (0.2), demonstrating that the dengue virus is more resistant to anionic β-D-glucans than the Herpes simplex virus. By comparison with a previous study on the antiviral activity of sulfonated botryosphaerans, we conclude that the presence of carboxymethyl groups might have a detrimental effect on antiviral activity.

【 授权许可】

Unknown