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

• Published in: International journal of molecular sciences Vol. 22; no. 20; p. 11013
• Main Authors: Lopes, José Louzinho, Quinteiro, Vinicius Seiki Takemura, Wouk, Jéssica, Darido, Maria Laura, Dekker, Robert F H, Barbosa-Dekker, Aneli M, Vetvicka, Václav, Cunha, Mário A A, Faccin-Galhardi, Ligia Carla, Orsato, Alexandre
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12.10.2021; MDPI
• Subjects: (1→3)(1→6)-β-D-glucan; Acids; Algae; Animals; anionic polysaccharides; Antiviral activity; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; antivirals; beta-Glucans - chemistry; beta-Glucans - pharmacology; Carbohydrates; Carboxymethylation; Cell Survival - drug effects; Chlorocebus aethiops; Coronaviruses; Cytotoxicity; Dengue fever; dengue virus; Dengue Virus - drug effects; Dengue Virus - physiology; Glucan; Glucans; Glucans - chemistry; Glucans - pharmacology; Glucose; Glycoproteins; Glycosaminoglycans; Heparan sulfate; Herpes simplex; herpes simplex virus; Herpes viruses; Herpesviridae - drug effects; Herpesviridae - physiology; Infections; Mammalian cells; Methylation; Mimicry; Polysaccharides; Severe acute respiratory syndrome coronavirus 2; Spectrum analysis; Sulfonation; Sulfonic Acids - chemistry; Vero Cells; Viral infections; Virus Internalization - drug effects; Viruses; β-Glucan; herpes simplex virus; antivirals; (1→3)(1→6)-β-D-glucan; anionic polysaccharides; dengue virus
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222011013

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.