In situ derived sulfated/sulfonated carbon nanogels with multi-protective effects against influenza a virus

Abstract

Pandemic of H1N1 infections are frequently reported around the world. Despite the availability of influenza remedies, the high tendency for influenza virus to mutate can lead to the emergence of drug-resistant strains. Additionally, the adverse effects of current anti-flu drugs have led some countries to implement restrictions on to use. In response to the urgent demand to explore and design novel antivirals, we have developed a potent alginate (Alg)-derived anti-flu material, from seaweeds. The preparation involves a one-step pyrolytic reaction of a mixture of sodium alginate and ammonium sulfite (AS), which forms carbonized nanogels (CNGs). We have characterized the chemical and physical properties of these Alg@AS CNGs, validated the anti-flu activity in vitro and in vivo, and explored the underlying mechanism. Our results indicate that the Alg@AS CNGs possess abundant sulfite/sulfate surface moieties, exhibit high biocompatibility and remarkable viral suppression properties against H1N1. The viral suppression of Alg@AS CNGs was found to be superior to other sulfated polysaccharides, such as fucoidan, carrageenan, and chondroitin sulfate. The administration of Alg@AS CNGs to H1N1-infected cells and mice resulted in higher cellular viabilities and mouse survival rates, respectively. Improved pathological indices were observed in lung sections, which showed substantially reduced gene expression of inflammatory mediators in tissues upon Alg@AS CNG treatment. We further showed that the Alg@AS CNGs could inhibit H1N1 infection by binding to viral particles and lowering the oxidative stress in cells. In summary, Alg@AS CNGs that were developed in this study were shown to exhibit potential anti-flu activity that protected animals from this lethal health challenge. These findings show that Alg@AS CNGs could be a potential candidate for future pharmaceutical development as an influenza remedy.