The Hindu News Update Service

News Update Service
Friday, April 20, 2007 : 1445 Hrs

Sci. & Tech.
Blood may hold clue to new HIV drug: researchers

New York, April 20. (PTI): A natural component of human blood has been found to 
block the HIV virus from infecting cells, raising hopes that a novel class
of drugs could be developed to fight the virus.

There is also evidence that HIV doesn't easily develop resistance to the new 
compound, which is a major problem with many current HIV treatments, researchers
said.

The molecule, known as VIRIP (virus-inhibitory peptide), binds to a spiky 
protein on the surface of the HIV virus called gp41. HIV normally uses this 
protein
to make the first contact with and latch onto a human cell, after which it 
would infect it. But the intervention of VIRIP stops that contact from 
happening,
it explained.

The molecule was found by Frank Kirchhoff of the University of Ulm in Germany 
and his colleagues, who report their work in the journal Cell.

They screened a massive library of compounds isolated from 10,000 litres of 
filtered human blood, looking for substances that could naturally inhibit HIV.
Human blood has yielded some HIV-inhibiting substances before, the report said.

Pinpointing exactly which compounds have an effect is difficult, lots of blood 
is needed to be able to single out and test enough of each compound found.
Kirchhoff's team had access to a large library of blood compounds at IPF 
PharmaCeuticals, a pharmaceutical company in Germany keen to develop the work.

Once they had isolated the protein, Nature magazine said, the team set about 
adjusting it to explore which changes to its structure might alter its function,
by fiddling with the amino acids in its 20-amino-acid chain.

In one instance, the researchers found that adding just one specific amino-acid 
building block rendered the protein useless in protecting against HIV. "We
were surprised it was so specific," says Kirchhoff adding "it is really 
striking."

Of the mass number of alterations the team tested, they found one instance in 
which altering just three specific amino acids made the compound 100 times
more effective at inhibiting HIV a potent drug candidate.

The group, the report says, has already tested this modified version in animal 
models, including rats, dogs and monkeys, to make sure it is not toxic. The
unpublished results look promising, Kirchhoff says, and the molecule could be 
ready for clinical trials by the end of this year.

Another bonus is that HIV should not be able to develop resistance to VIRIP as 
easily as it can with other drug compounds.

Half of the patients given a drug called T20, for example, which also acts to 
prevent HIV entering the cell, develop resistance to it, Neelanjana Ray, a
virologist at the University of Pennsylvania in Philadelphia, is quoted as 
saying.

This is because HIV has proven to be very adaptable; many of its surface 
proteins constantly change. But VIRIP picks on a fairly stable surface protein,
which does not change so much - it works in conjunction with another protein, 
called gp120, which was recently discovered to be conserved over time.

This means that drug using it should remain effective. "The really good thing 
is that it targets a very conserved area," says Ray adding "It does seem to
be a promising candidate."

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