Synthetic effective drug against latent HIV

Representatives of a new family of biologically active molecules, called brijologists, operate secret "reservoirs" containing latent HIV, which otherwise make the disease completely inaccessible to antiretroviral drugs.

Thanks to antiretroviral drugs for almost twenty years, the diagnosis of "AIDS" is not a death sentence. At the same time, highly active antiretroviral therapy (VAAT) still does not lead to a complete cure. In this case, patients must strictly adhere to the regular regimen of taking medications with many side effects. And if, for example, even in the US, the passage of such a lengthy procedure is difficult (financially), then in developing countries it is practically impossible.

The main problem with VAAT is that it is not able to reach the virus that is hidden in so-called proviral reservoirs - T-cells, inside of which there is a hibernating HIV. Even after all active viral particles are exterminated, skipping just one antiretroviral drug intake can lead to the fact that the virus that was before in hibernation again turns into an active state and instantly attacks the host's organism, and the medicine that has been applied until now ceases to function! Until now, no one has been able to offer a tool that can at least somehow affect the HIV-infected cells.

But scientists from the laboratory of Paul Wender (Paul Wender), working at Stanford University (USA), it seems, have come very close to solving the problem.

Researchers synthesized a whole library of Brijologists, whose structure is based on a very inaccessible natural substance. As has been shown, new compounds successfully activate latent HIV-reservoirs with an efficiency equal to or superior to that of a natural analogue. I want to believe that the results of this work will finally give doctors an effective tool with the help of which it will be possible to completely eradicate the hated virus from the body. The research report is presented in the journal Nature Chemistry.

And a little about how it all began ... The first attempts to achieve reactivation of the latent form of HIV were inspired by observations of the "work" of healers from the Samoa archipelago. Having conducted a thorough study of the bark of a mammal tree growing in Samoa and traditionally used to treat hepatitis, ethnobotanists have found that it contains the biologically active component of prostratin. The substance activates the protein kinase-C-enzyme, which forms the signal pathway necessary for the reactivation of the latent virus. Later it was shown that prostrate is not the only and not the most effective molecule, capable of binding to kinase.

Bugula neritina, a bryophyte colonial sea organism, synthesizes a much more efficient protein kinase-C activator than prostratin. Scientists believed that this molecule, called braiostatin-1, has a great potential not only to combat HIV infection, but also in the treatment of cancer and Alzheimer's disease. And everything would be fine, but the begun clinical trials had to be canceled because of the extreme inaccessibility of this natural preparation. The fact is that to obtain only 18 g of braiostatin it is necessary to process 14 tons of Bugula neritina living organism. The National Cancer Institute, which conducted the tests, decided to wait until the available method for obtaining a synthetic analogue is developed.

For the creation of the method of obtaining briostatin, Professor Wender's scientific group took the task, in the laboratory of which the synthesis of prostratin and its analogues was previously developed. As a result, the scientists managed to offer a very effective approach to the synthesis of briostatin and its six non-existent analogues. In laboratory tests on special samples of infected cells, it has been shown that briostatin and its analogs are 25-1,000 times more effective than prostastin. In addition, in in-vivo experiments in animal models, these substances demonstrated complete absence of toxic effects.