Alternate methods
Channel: Ian Crossland
Date: 01/11/2007

http://news.yahoo.com/s/afp/20071026/hl_afp/healthdiseaseaids

Fri Oct 26, 4:17 AM ET

PARIS (AFP) - A prototype drug, tested on lab-dish samples of the AIDS virus, has shown great promise in attacking HIV from an unprecedented direction, French researchers reported on Friday.

The drug inhibits the human immunodeficiency virus (HIV) at a key point -- when it uses the hijacked machinery of an infected immune cell to reassemble its genetic code.

This process, called splicing, joins together sections of viral code to form pre-messenger RNA, which is a precursor for messenger RNA (mRNA).

This molecule provides the blueprint for cranking out viral proteins and enzymes which are essential for replication.

Once these are created, baby viruses can be reproduced en masse within the cell, eventually breaking out and heading into the bloodstream, where they go on to infect other cells.

The scientist found that a test molecule, called IDC16, interferes with a human splicing protein called SF2/ASF that is used to do the pre-messenger RNA cut-and-paste.

As a result, the reproduction process was braked at the start.

In lab-dish tests, IDC16 blocked replication of different strains of HIV-1, including samples from patients who are resistant to the famous "cocktail" -- combination therapy -- of anti-HIV drugs.

The paper appears in the US open-access journal Public Library of Science (PLoS) Pathogens.

In a press release, France's National Centre for Scientific Research (CNRS), which is backing the project, said IDC16 was "extremely promising."

The "cocktail," first introduced in 1995, has been a lifeline for millions of people by attacking the protein gp120, which is on the surface of the virus, and enzymes that are used in other phases of the replication process.

The problem, though, is that HIV mutates, making these proteins a shifting target for drug engineers.

The authors, led by Jamal Tazi of the Institute of Molecular Genetics in Montpellier, are confident that IDC16 throws up a way of sidestepping mutation.

"Instead of attacking the components brought along by the virus, we use the machinery that it uses in the cell," Tazi told AFP.

By aiming at splicing, other viruses could be targeted, Tazi added.

"These findings may serve as the basis for a new strategy to develop a new class of anti-HIV drugs, the splicing inhibitors, and even of antiviral drugs in general, since any virus needing to splice its RNAs may be targeted," his team writes.

However, exhaustive tests on lab animals, leading to cautious trials on humans, are needed before IDC16 can be certified as safe and effective. This process typically takes years."