Clinical and Public Health Microbiology

Treatment Breakthrough Will Block Both Known Viruses and New Viruses

A protein called NOX2 oxidase is activated by viruses and suppresses the body’s key antiviral reaction in a part of the cell called the endosome.  Now a team of researchers based at eight universities across Australia with colleagues in the United States and Dublin, Ireland have found a drug called Cgp91ds-TAT that is given intranasally and blocks NOX2’s action in the influenza virus, reducing disease severity by around 40 percent.  If it also blocks the action of other endosome-transmitted viruses, a new era of treatment for viral diseases may have begun.

Endosomes are small organelles in the cell membrane that sort outside substances into tracks and send them to the parts of the cell that need them.  Endosome-transmitted viruses include pathogens as diverse as rhinovirus that causes the common cold, influenza viruses, Dengue fever, and HIV.  NOX2 oxidase is primarily found in the endosome and blocking its activity only affects viruses that enter through this pathway.  Other viruses, including the mumps virus and Newcastle disease virus, enter cells through a fusion process with the cell membrane and are not affected by blocking NOX2.

However, because NOX2 oxidase is part of an essential viral mechanism, blocking it may allow us to interfere with new endosomic viruses that evolve and enter the human population in the future, regardless of their strain, without having to create virus-specific vaccines.

First author Eunice To and senior author Stavros Selemidis at RMIT University in Melbourne collaborated with Doug Brooks from the University of South Australia, also in Melbourne, John O’Leary from Trinity College in Dublin, Christopher Porter from Australia’s Monash University and a variety of others on this work.  The team is currently looking for other drugs to block NOX2 oxidase that will expand the potential of their discoveries as far as possible.

For more information, go to the July 12 issue of Nature Communications 8, Article number: 69 (2017); doi:10.1038/s41467-017-00057-x.