Researcher says physics may outsmart viruses

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When a virus infects another cell, it inserts its genetic material into the cell and hijacks it to make extra copies of the virus.

That process, Alex Evilevitch has learned, is more like an artillery barrage than a stealth attack.

The way many viruses transfer their genomes into host cells is by ejecting them with a force 10 times greater than the explosion of a champagne cork, the Carnegie Mellon University physics professor said.

The Russian-born scientist, who joined CMU last year from Lund University in Sweden, is a leader in the growing field of physical virology, which studies the physics of viruses.

As he works to unravel the mechanical and electrical forces that govern viruses, Dr. Evilevitch hopes one day to develop medical treatments that can't be outsmarted by the rapidly mutating organisms.

To give just two examples where this is now a problem, he cited AIDS and the flu.

The standard treatment for HIV infections today is antiretroviral medications, which hamper the ability of the virus to transcribe its genetic material inside human immune cells.

"But the virus mutates eventually and the medication stops working," he said. "That has been one of the main difficulties with antiviral therapies today."

With the flu, one of the main treatments after someone has the illness is the antiviral medication Tamiflu. It acts by inhibiting the ability of an infected cell to release new copies of the flu virus.

But once again, he said, some flu strains have figured out how to sidestep Tamiflu, lessening its effectiveness.

Drugs like the antiretrovirals and Tamiflu "are highly specific" to different diseases, "so they can be very efficient, but the viruses mutate and then the medications stop working."

The overall problem with these medications is that they are like a football defensive squad trying to tackle individual players on the virus's team, only to discover the virus has substituted players that can break through their defenses.

To get around that flaw, Dr. Evilevitch hopes to develop methods that in effect would keep the virus's team out of the stadium altogether. Specifically, he wants to shut down or severely limit the forceful ejections that viruses use to infect cells.

The tremendous force comes from the fact that the virus's genetic material and water molecules are packed tightly inside protein capsules.

In the case of viruses that infect bacteria, known as bacteriophages, his team has shown that when a tail on the virus docks with a receptor on the outside of a bacterial cell, it opens a portal that allows the viral DNA to spew out.

With some viruses that infect animal and human cells, the entire protein capsule gets inside a cell and then ejects its DNA after it links up with the cell's nucleus.

The DNA inside a virus has a distinct negative electrical charge, he said, so one way to thwart the virus might be to find small positively charged molecules to counteract that.

"If we can find a small peptide with a positive charge and this can interact with the negative charge, it might either keep the DNA inside the [capsule] or decrease the strength of its release."

One other possible way of dampening the virus's ejection force would be to find targeted polymers or other molecules that could suck water out of the virus's interior, he said.

Dr. Evilevitch said he and fellow researchers are probably years away from developing these therapies for human trials.

But if they succeed, they may have figured out a way to thwart the marvelously insidious ability of viruses to keep mutating, and keep making us sick.

Mark Roth: or 412-263-1130.


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