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

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)-ß-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 ß-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.

Virus Infections and Host Metabolism-Can We Manage the Interactions?

When viruses infect cells, they almost invariably cause metabolic changes in the infected cell as well as in several host cell types that react to the infection. Such metabolic changes provide potential targets for therapeutic approaches that could reduce the impact of infection. Several examples are discussed in this review, which include effects on energy metabolism, glutaminolysis and fatty acid metabolism. The response of the immune system also involves metabolic changes and manipulating these may change the outcome of infection. This could include changing the status of herpesviruses infections from productive to latency. The consequences of viral infections which include coronavirus disease 2019 (COVID-19), may also differ in patients with metabolic problems, such as diabetes mellitus (DM), obesity, and endocrine diseases. Nutrition status may also affect the pattern of events following viral infection and examples that impact on the pattern of human and experimental animal viral diseases and the mechanisms involved are discussed. Finally, we discuss the so far few published reports that have manipulated metabolic events in-vivo to change the outcome of virus infection. The topic is expected to expand in relevance as an approach used alone or in combination with other therapies to shape the nature of virus induced diseases.