New compound nearly wipes out HIV in cells

Derived from a marine sponge, the substance could form the basis of a new class of HIV anti-virals
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Cortistatin A is proving its mettle, only 6 years after researchers first isolated the compound from a marine sponge. The substance appears to virtually wipe HIV from infected cells, according to a new study by scientists at The Scripps Research Institute's Florida campus.

Details are published in the July 20 issue of the journal Cell Host & Microbe.

Scientists are hopeful because they believe that Cortistatin A will define a new class of HIV anti-viral drugs that not only combats the virus, but also represses replication of the virus in cells both acutely and chronically infected. Existing drugs decrease the viral load, sometimes to undetectable levels, but don't eliminate the virus itself, the research team explains.

For the study, Scripps Research scientist Susana Valente and her group used a synthetic version of didehydro-Cortistatin A to study how it would affect two different strains of HIV: HIV-1, the most common, and HIV-2, which is found in West Africa and certain sections of Europe. In their test, they found that the compound beat back HIV production 99.7% from primary CD4+T cells that had been isolated from patients who had undetectable levels of the virus in their bloodstream and had been treated for a while with Highly Active Anti-retroviral Therapy.

The compound worked even better when added to additional anti-viral treatments. In this scenario, it helped slash by another 20% the viral replication from CD4+T cells isolated from patients that had detectable virus levels in their blood.

Drug developers may also want to take note here. The compound appears to work by binding to the Tat viral protein, which activates HIV gene expression. In doing so, the mechanism stops the virus from replicating itself even at really tiny concentrations. Valente said in a statement that the compound is already the most potent anti-Tat inhibitor so far, and withdrawing the drug from cell culture doesn't leave the virus rebounding as it does in other anti-retrovirals. What's more, the inhibitor is also effective at low concentrations and appears to have no toxicity connected to it at the cellular level, according to the study.

The compound is a long way from human trials, but the early testing--funded by the National Institutes of Health's National Institute of Allergy and Infectious Diseases (NIAID) and the Landenberger Foundation--is promising and warrants future work.

- read the release
- check out the study summary

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