DRACO: A Cure for the Flu Season?

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Today, in spite of advances in research and medicine, viruses continue to be a major health problem. Part of the problem is that viruses evolve quicker than new vaccines can be created to keep viruses at bay. Relative to human evolution, viruses mutate and replicate at an astonishing rate into strains and sub-strains that are vaccine-resistant. Rhinoviruses responsible for the common cold for example, more often than not, thumb their metaphorical noses at the latest seasonal flu vaccine. However, their comeuppance may be here. In a recent article in the scientific journal PLoS One, researchers at MIT may have created a silver bullet that will kill not just one flu virus type, but potentially almost all viruses.

The Milkmaid Observation

In 1796 an English country doctor named Edward Jenner inoculated 8-year-old James Phipps with cowpox virus using the pus from the hands of Sarah Nelmes. Sarah was a milkmaid who contracted cowpox from an infected dairy cow.

At the time, human smallpox infection was ubiquitous and occurred frequently. However, one known observation was that milkmaids who contracted cowpox never seemed to catch smallpox. Cowpox would manifest as rashes on the milkmaids’ hands that then became pus-filled before scabbing over and eventually healing. This was a nuisance for the milkmaids, but never fatal. Basing his experiment on this observation, Jenner hypothesized that the pus from the udders of infected cows somehow protected the milkmaids from ever becoming infected with smallpox.

Jenner inoculated Phipps a second time several weeks later with a live smallpox virus. After repeated smallpox inoculations on the boy with no signs of smallpox infection resulting, Jenner proclaimed that the milkmaids were immune to smallpox and that the immunity can be passed on from man to man. Jenner (and the boy) was fortunate that the milkmaid/cowpox observation was the causation in conferring immunity to smallpox. As it turns out cowpox and smallpox are closely related viruses.

Viral Wars: attack, counterattack, counter-counterattack

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Although cowpox and smallpox are closely related, the majority of viruses are not. This is why there has not been a single vaccine to date to combat all viral infections. However, viruses do have a commonality: unlike humans and animals the genetic structure of most viruses is single-stranded or double-stranded RNA rather than double-stranded DNA.

When a virus infects a human cell, it essentially takes over the replication machinery within the cell and proceeds to manufacture copies of its viral genome. Human cells typically have natural defense mechanisms that detect foreign double-stranded RNA and act to destroy the RNA. However, viruses can often counter these defenses.

In the Lincoln Laboratory at MIT, researchers came up with a novel way of countering the viruses’ counter attack. What they did was create a chemical silver bullet they named “Double-stranded RNA Activated Caspase Oligomerizer” (DRACO). DRACO is a chimeric protein that has three parts. One part is a protein transduction tag that allows the chimera to enter all cells—even across the blood-brain barrier. The second part is a protein that recognizes and binds to viral double-stranded RNA. And the third part is a special caspase protein that becomes activated when two more of the DRACO chimera proteins bind to the same double-stranded RNA and crosslink with each other.

The caspase protein, when activated by the crosslinking, induces cell death and thereby destroys the virus-infected cells. Only cells that are infected with double-stranded viral RNA will undergo cell death. All other cells that the DRACO chimera enters that are not infected with a virus will remain unharmed.

Antiviral Protein Promising Results

To date, the researchers have tested their DRACO antiviral protein chimera against 15 different viruses—including the H1N1 influenza virus. In mice infected with H1N1, their research demonstrated that inoculating the infected mice with DRACO resulted in rescue of the mice. In addition, their research has shown that their DRACO therapy is nontoxic in 11 mammalian cell types.

The significance of this research is multifold. A first-of-its-kind antiviral therapy that is broad spectrum, effective and safe may become the biggest medical advancement in immunology since the day Jenner experimented on his gardener’s son. Future studies will continue with animal testing until clearance for human trials is granted. The real test, however, will be to see if viruses will be able to eventually mutate against this new weapon in mankind’s war against viruses.

Source: Rider TH, Zook CE, Boettcher TL, Wick ST, Pancoast JS, et al. (2011) Broad-Spectrum Antiviral Therapeutics. PLoS ONE 6(7): e22572. doi:10.1371/journal.pone.0022572

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