26 May 2008

HIV can be dealt with in a different way

Scientists at the University of Michigan, working under the guidance of Professor Heather Carlson, have developed a mechanism that, according to their statement, is the first new approach in the last 20 years to block the traditional target of HIV treatment/AIDS is an HIV protease enzyme necessary for virus replication. The authors believe that their discovery may give rise to a new class of drugs for the treatment of HIV infection.

Using computer modeling, scientists have created a compound that blocks HIV protease due to a fundamentally new mechanism. The effectiveness of the compound has been confirmed in laboratory experiments, however, according to Carlson, it is not active enough for successful functioning in the body.

The principle of action of modern drugs of the protease inhibitor class is to inactivate the HIV protease and prevent virus replication. The new compound has a similar effect, but the result is achieved by a different method.

Protease is necessary for the processing of proteins, from which a viable viral particle is subsequently assembled. Traditional drugs are large molecules that connect to the center of the enzyme molecule, completely neutralizing it.

The new mechanism acts on another region of the HIV-1 protease molecule, the flap recognition pocket (this can be translated as "detector and pocket valve").

Scientists knew before that the "pockets" in the structure of the protease molecule open and close, but until now they have not been able to influence these mechanisms.

The authors found that blocking the "pocket" in the open position with the help of a small molecule synthesized by them (two times smaller than the molecules of traditional protease inhibitors) it also inhibits the enzyme.

In the video in the University of Michigan press release, you can see how this molecule moves between the protease sites, preventing the "pocket closure" – the assembly of the enzyme molecule into the active form.

The attractiveness of small molecules as drugs is due to the fact that, compared with large molecules, they are better absorbed by the body, their effectiveness is usually higher, and the probability of side effects is lower.

However, the authors emphasize that it is much easier to synthesize an inhibitor that works in vitro than an effective drug for the treatment of humans, so their discovery is, although very significant, but a preliminary stage of work.

Article by Kelly L. Damm et al. A poke in the eye: Inhibiting HIV-1 protease through its flap-recognition pocket is published in the journal Biopolymers.

Portal "Eternal youth" www.vechnayamolodost.ru22.05.2008

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