There have been a few important successes in antiviral drug development, but for the most part it is extremely difficult to find drugs to treat viral infections. Viruses are highly effective hijackers of cellular processes, and since drugs that target cellular processes are likely to be toxic, that leaves only a few potential virus specific targets. Further, because of the diversity of viruses most antiviral drugs are very specific for their target virus and are not effective against others. The holy grail of antiviral drugs would be something that inhibits replication of many viruses – a broad spectrum antiviral.
A new paper in PLOS One describes a creative approach to the problem of broadly targeting viral infections. The approach uses a recombinant protein that combines the properties of two natural antiviral response pathways in the cell. Almost all viruses generate long double stranded RNA (dsRNA) at some point in their replication cycle. But long dsRNA is not found in normal, healthy cells. So the presence of dsRNA triggers a response in the cell that shuts down gene expression, which can effectively shut down viral replication. Another response is apoptosis: an infected cell can trigger a cellular suicide pathway, destroying the infected cell and the virus along with it. In this new study, researchers fused parts of proteins from key mediators of both pathways to generate a new protein called DRACO that triggers apoptosis when it binds to dsRNA.
In cell culture, DRACOs induce apoptosis in cells only when dsRNA is present. The study goes on to test whether DRACOs can protect cells from infection. Cells pre-treated with DRACOs survive viral infection, while untreated cells don’t. And it protects against a large variety of different viruses; viruses from 7 different families were tested and DRACOs appear to be effective against all of them. But for an antiviral to be useful it has to also work in vivo, and DRACOs show some promise here too. 60-70% of mice pre-treated with DRACOs survive influenza virus challenge, while only 10% of untreated mice survive.
The results of this study are exciting and show promise but we must be cautious about over-extending the findings. It is a long and challenging process to go from an early stage development like this one to a clinically useful anti-viral drug. There will be some very significant hurdles to overcome to develop this further. In all the experiments, the cells (or animals) are pre-treated with DRACOs, but its not known if there is any post-exposure protection. The animal studies show that interperitoneal injection can protect animals, but the distribution of the drug in different tissues varies and in some tissues disappears before 24 hours, which could be a problem if it can’t reach the required concentrations in the target tissues. Also, being a protein, there will be challenges for effective delivery (since interperitoneal injection is not likely to be a favored route!). Many years of further testing, development, and clinical trials (if it gets that far) are needed. Despite the many challenges that lay ahead for further development of this broad spectrum anti-viral, it appears promising and worth pursuing.
As usual though, news reports describing this as a major breakthrough have missed the point that this is an interesting new development but that it is very much in its infancy. Since nearly every discovery is hailed as a breakthrough, the public gets a distorted idea of the way science proceeds. Media reports have also been misleading, including promoting it as a potential treatment for HIV or Hepatitis, which weren’t even among the viruses tested, or touting it as a possible cure for nearly all viral infections. Slow down a little, folks. There is a long way to go before those claims can be made. Perhaps someone can develop a treatment for the disease that makes headline writers distort information.
