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Genetic Engineering

If You Can't Beat Viruses, Mimic Them

14 years, 6 months ago

814  0
Posted on Apr 03, 2004, 7 a.m. By Bill Freeman

Benign molecules hijack cells so that viruses can't By Gabe Romain, Betterhumans Staff A new type of antiviral agent has been developed that mimics viruses to stop them from infecting cells or becoming drug resistant. Developed by researcher John Yin and colleagues at the University of Wisconsin-Madison, the antiviral molecules copy the machinery that viruses use to replicate.
Benign molecules hijack cells so that viruses can't
By Gabe Romain, Betterhumans Staff

A new type of antiviral agent has been developed that mimics viruses to stop them from infecting cells or becoming drug resistant.

Developed by researcher John Yin and colleagues at the University of Wisconsin-Madison, the antiviral molecules copy the machinery that viruses use to replicate.

"When a virus encounters a susceptible cell, it enters and says, 'I'm now the boss,'" says Yin. "It pirates the cell's resources to produce virus progeny that, following release from the host cell, can infect other cells."

The antiviral molecules could prevent this cascading process.

Cellular pirate

A virus is a nucleic acid enclosed in a protein coat or capsid that infects biological organisms by hijacking their cellular machinery.

Once a virus has infected a cell, it commandeers its ribosomes, enzymes and other parts to reproduce.

Because they use the machinery of their host cells, viruses are difficult to kill.

Current antiviral approaches use drugs that bind to and block the function of virus proteins&emdash;molecules viruses produce to help with replication.

While this method is sometimes successful in knocking out key functions that viruses use to grow and reproduce, it doesn't always work, says Yin.

"When a virus reproduces, it doesn't do so perfectly," he says. "Sometimes, it inserts genetic typos, creating variations that may allow some versions of the virus proteins to develop an evolutionary advantage, such as drug resistance."

Parasitic particles

To overcome such problems, Yin and colleagues took a different approach.

They created a molecule that imitates parasitic viruses by entering cells and taking over the machinery that viruses require for growth.

The molecules are smaller, faster and more stealthy than actual viruses, and they don't encode any virus proteins, which renders them powerless inside a cell, says Yin.

The researchers analyzed the potency of this approach in computational models in which the bacteria E. coli had been infected with a particular virus.

For their theoretical molecule, they introduced a short piece of RNA that competes for the same resources as the infectious virus.

Without this molecule, the virus produced more than 10,000 copies of itself in less than 20 minutes after infection.

In the presence of the molecule, the virus had no new progeny.

"The parasitic strategy outperformed the non-parasitic strategies at all levels," says co-researcher Hwijin Kim. "It inhibited viral growth, even at a low dose, placed minimal demands on the intracellular resources of the host cell and was effective when introduced either before or during the infection cycle."

Resistance is impossible

In addition, there is no obvious way in which the approach could cause the development of drug-resistant strains of viruses.

"Our calculations suggest that this antiviral strategy is a very effective approach and one that is very difficult for a virus to overcome," says Yin. "There are definite technical challenges to implementing this approach, but the findings do open the door to a broader way of thinking about antiviral strategies."

Yin says the next step will be to test the antiviral strategy inside living cells.

The research is reported in the journal Antimicrobial Agents and Chemotherapy (read abstract).

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