Could targeting ROS enzyme provide a broad antiviral strategy?

Collaborative research led by RMIT University (Melbourne, Australia) has identified a host enzyme, NOX2, that appears to exacerbate viral pathogenicity, and the study has suggested that targeting this mechanism could provide an antiviral strategy for a wide range of infections.

The imminent threat of viral pandemics has led to calls for treatments that can act against multiple infections, regardless of the infecting viral strain. Senior author Stavros Selemidis (RMIT University) explained: “Current treatment strategies are limited as they specifically target circulating viruses and have either unknown or very little effect against new viruses that enter the human population.”

This study, published recently in Nature Communications, aimed to try and uncover the action of reactive oxygen species (ROS) in humans. ROS are known to protect plants, fungi and some animals from invading pathogens; however, in mammals the reverse is reported, with ROS production linked to increased viral pathogenic activity.

The researchers identified the primary enzymatic source of ROS in humans, NOX2 oxidase. They observed that that NOX2 oxidase, which is housed in endocytic compartments, is activated by single stranded RNA and DNA viruses such as flu, dengue and HIV.

The team demonstrated that once activated, NOX2 oxidase generates hydrogen peroxide, which in turn supresses key antiviral reactions via the modification of Toll-like receptor-7, allowing stronger and more virulent disease in mice.

It was also demonstrated that targeted inhibition of this enzyme, via a prototype drug, reduced influenza A pathogenicity in murine models. Selemidis commented: “We have identified a protein of the immune system that contributes to the disease caused by flu viruses irrespective of their strain. We also developed a novel drug delivery system to target this protein, which drastically alleviated the burden of viral disease.”

This study is the first to report that endosomal NOX2 oxidase is activated by infecting pathogens, and exacerbates viral pathogenicity. In addition these findings suggest this enzyme could be an antiviral target with impactions for broad range of disease.

First author, Eunice To (RMIT University), concluded: “This work identifies a treatment strategy that has the potential to alleviate the symptoms caused by some of the most devastating viruses worldwide, including the flu.”

Sources: To EE, Luong R, Halls ME et al. Endosomal NOX2 oxidase exacerbates virus pathogenicity and is a target for antiviral therapy. Nat. Comms. 8 (69) doi:10.1038/s41467-017-00057-x (2017) (Epub);



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