Friday 19 October 2012

Virus Behavior Insight Offers Hope For New Drugs

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Main Category: Infectious Diseases / Bacteria / Viruses
Article Date: 19 Oct 2012 - 13:00 PDT Current ratings for:
Virus Behavior Insight Offers Hope For New Drugs


An important stage in the life-cycle of viruses such as the common cold and polio has been discovered by experts at the University of Leeds. This breakthrough may pave the way for new methods of battling viral diseases.


According to the study, published in the Proceedings of the National Academy of Sciences (PNAS), the researchers were the first to notice, at anatomic level, how the genome that creates the core of a single-strand RNA virus particle accumulates in its outer shell of proteins.


Accepted thinking about the process has been overturned by these results, lead researcher Professor Peter Stockley said. This could be a way into exploiting a chink in the armor of several types of viruses.


Stockley said, "If we can target this process, it could lead to a completely new class of anti-virals that would be less likely to create resistant viruses than existing drugs, which tend to target individual proteins."


Certain viruses, such as polio and the common cold have genetic material made up of ribonucleic acid (RNA) instead of DNA. The recent findings have discovered that the RNA in the viruses have considerably more volume than the virus particles made after they are "packed" inside their protein shell.


Dr Roman Tuma commented:


"We realized that the RNA genome must have to be intricately folded to fit into the final container, just like when you pack to go on holiday and need to fold your clothes to fit into the space in your suitcase."

When proteins were added to the viral RNA by the researchers, they observed an instant fall in the RNA's volume.


"It seems that viral RNAs have evolved a self-folding mechanism that makes closing the 'viral suitcase' very efficient. It's as though 'the suitcase' and the clothes' work together to close the lid and protect the content," Tuma said.


Stockley added, "The viral RNAs, and only the viral RNAs, can do this trick of folding up to fit as soon as they see the 'suitcase' coming. That's the important thing. If we can interfere in that process we've got a completely novel drug target in the lifecycle of viruses."


He continued:


"At the moment there are relatively few antiviral drugs and they tend to target enzymes that the virus encodes in its genome. The problem is that the drugs target one enzyme initially and, within the year, scientists are identifying strains that have become resistant. Individual proteins are extremely susceptible to this mutation. A fundamental process like the one we're looking at opens the possibility of targeting the collective behavior of essential molecules, which could be much less susceptible to developing resistance.

The report adds that the same effect is seen in plant and bacterial viruses as well. Stockley said, "While we have not proved it yet, I would put money on animal viruses showing the same mechanism too."


Researchers utilized state of the art machinery tailor-made at the University which let them to produce the first single-molecule measurements of viral assembly ever. This allowed the experts to analyze the viral particles individually. "The specific collapse, which can only be seen in such assays, was totally unexpected and overturns the current thinking about assembly," said Stockley.


Stockley concluded:


"We're now perfectly positioned to pursue questions about how this mechanism works in other viruses and we're already thinking about ways to start designing new antiviral drugs that would target this newly recognized feature of viral lifecycles."

Written by Christine Kearney
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

Visit our infectious diseases / bacteria / viruses section for the latest news on this subject. Evidence that viral RNAs have evolved for efficient, two-stage packaging
Alexander Borodavka, Roman Tuma, and Peter G. Stockley
PNAS, October 2012, doi:10.1073/pnas.1204357109 Please use one of the following formats to cite this article in your essay, paper or report:

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