06 April 2012

New Approaches in Anti-Viral Warfare: Hope for HIV, HepC, HSV ...?

Here are three promising new approaches to meeting the threat of the viral apocalypse:
  1. Teach the body to throw a "monkey-wrench" into the virus assembly, preventing the virus from forming
  2. Devise a "super-interferon" broad spectrum super-antiviral
  3. Teach cells that are infected with dangerous viruses to commit suicide

Buoyed by advances in molecular biology, a handful of researchers in labs around the US and Canada are homing in on strategies that could eliminate not just individual viruses, but any virus, wiping out viral infections with the same efficiency that penicillin and ciproflaxacin bring to the fight against bacteria. If these scientists succeed, future generations may struggle to imagine a time when we were at the mercy of viruses, just as we struggle to imagine a time before antibiotics.

Three teams in particular are zeroing in on new antiviral strategies, with each taking a different approach to the problem. But at root they are all targeting our own physiology, the aspects of our cell biology that allow viruses to take hold and reproduce. If even one of these approaches pans out, we might be able to eradicate any type of virus we want.

...The first thing researchers at Prosetta had to do was search for promising candidates -- molecules of just the right shape to lodge into the capsid-making machinery. They screened 80,000 compounds by testing each in a cell-free system. Most couldn't stop capsids from forming, but a few dozen did. Instead of focusing on one, Lingappa decided to pursue almost all of them on the premise that a victory against any one virus would help Prosetta extend its strategy to all of them.

It was a gutsy strategy, and so far it's paying off. Studies -- in both cell cultures and on animals -- are showing that Prosetta's approach can stop rabies, Ebola, influenza and a number of other viruses. If, as Lingappa suspects, all viruses need help from their host cells to assemble, he may have found a strategy that can work against every virus that could ever make us sick.

[The] second approach is being spearheaded by Eleanor Fish of the University of Toronto. She and other researchers worldwide are developing drugs that might replace or supplement interferons, our own catch-all viral response proteins. Essentially the idea is to accelerate the body's own virus-killing powers. Our cells can sense a viral invasion because of a quirk in the way most viruses replicate: using the host cell's machinery, they copy their own genes by making a peculiar molecule called double-stranded RNA. So our cells are equipped with proteins whose sole job is to detect double-stranded RNA. When they do, they relay a signal throughout the cell that an intruder has invaded.

The cell then produces interferons, which in turn trigger the production of more than 300 other kinds of proteins, each with its own role to play in killing viruses. Some slice up the virus's genes and wreck its proteins. Others tell the cell to become rigid, making it harder for new viruses to escape. The infected cell also sends interferons to surrounding cells, creating a firebreak that stops the spread of the infection. "The very first response to a virus is an interferon response," Fish says.

...By tacking on polyethylene glycol -- a cluster of hydrogen, carbon and oxygen atoms -- they've created synthetic interferons that last days instead of hours and will wipe out hepatitis C viruses completely in up to 81 per cent of treated patients, depending on the strain. During Toronto's Sars outbreak, Fish tested synthetic interferons on a small pool of patients and found that their lungs healed significantly faster than those of control patients, allowing them to get off supplemental oxygen sooner. Like Lingappa, Fish has huge ambitions for these synthetics. If one of them succeeds, it could become a single drug to fight not just one virus or a few, but nearly every virus.

...The third and arguably the most radical approach to broad-spectrum antivirals was conceived years ago by biological engineer Todd Rider... "I wanted a treatment that was broad spectrum, that was effective against a wide range of viruses, and that would be difficult for viruses to evolve resistance to," he says.

That something was an artificial protein. To make it, he would need to marry parts of two natural proteins. One string would detect double-stranded RNA, the telltale sign of most invading viruses. The other would lead the infected cell to kill itself. Rider wanted to make a poison pill for cells: a protein that, when it grabbed on to the double-stranded RNA of a virus, would trigger instant cellular suicide. That may sound like a dangerous kind of therapy, but our bodies already rely on it naturally to fight both infections and cancer.

Rider dubbed his theoretical molecule Draco, for double-stranded RNA activated caspase oligomeriser. _Wired
These approaches represent a departure, of sorts, from conventional consensus antiviral approaches. Sceptics of traditional approaches, scientific mavericks blaze new trails of discovery which their orthodox "safety in the crowd" colleagues would never risk.

The fact that it has taken so long for humans to begin to devise such strategies, in the face of desperate need, suggests that human educators and human societies are not raising children who can make use of their innate intellects and creativity. The brains that we have are being wasted, and the brains that we could have are not imagined or conceived. The intellectual powers we do have are too often squandered on consensual orthodoxies, intellectual treadmills to nowhere.


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