Broad Spectrum Antiviral is an Effective Inhibitor of Viruses but Not Media Hype

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.


4 thoughts on “Broad Spectrum Antiviral is an Effective Inhibitor of Viruses but Not Media Hype”

  1. This seems to be an interesting and efficient approach! Although it is not something that our immune system would naturally do. And how the protein is going to make its way into the cellular membrane is exactly what we are talking about recently!

  2. Thanks Ed, thats a good point. And it would definitely need to be tested for efficacy post-symptom development. But even if it didn’t work after showing symptoms, if it works pre and post-exposure it could be used as a prophylactic to quell an outbreak but administering it to potential contacts. I still think one of the big challenges will be delivery of the drug. Do those tags work in humans? I seem to recall that they are inconsistent in their ability to deliver proteins across membranes.

  3. I was just looking at the data again and it seems slightly more promising than I first thought. In the final figure they treat mice i.n. at day 0, i.e. the same time as infection with 1LD50 of H1N1, and see excellent protection. 50% (1LD50) of untreated (buffer) mice die by day 10, whereas between 80 and 100% of treated mice survive up to this time point. Granted the experiment did not go on longer and we were not shown data regarding the morbidity of the mice, weight loss for example. However, for a single dose – that appears not to persist in the lungs much beyond 24 hours – prophylactic treatment against influenza virus this is good. Just need to see if DRACO can be effective when administered post-symptom expression, which is when it would most likely be given if it makes it to market.

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