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Toward a Functional Cure for HIV, with Help from Drug Discovery Under the Sea

Sep 23, 2015 1:00:32 PM / by Maria

Thanks to a marine sponge, a novel way of combating HIV latency may have been found.

In 1984, HIV was identified as the virus that causes AIDS. About a decade later, drugs came on the scene that changed the outcome of HIV from fatal to manageable. Now two more decades have passed, and despite all we've learned in the life sciences, a cure and a vaccine are yet to come. What will it take for at least a functional cure?

HIV The oceans abound with potential cures, including a possibly novel solution to HIV. Image credit: commons.wikimedia.org

The problem is HIV latency. In patients taking antiretroviral therapy, HIV persists in the genomes of resting CD4+ T cells. Low-level basal reactivation keeps the virus humming along beneath the surface. Patients who discontinue therapy will almost certainly experience a full viral rebound.

A potential solution originated in our oceans. The marine sponge Corticium simplex was found to generate steroid-like molecules called cortistatins. Cortistatin A was demonstrated to have antiproliferative activity; the focus was thus first on cancer. Because cortistatin A is in scarce supply, and because synthesizing it is not trivial, scientists came up with a simpler analog, didehydro-Cortistatin A (dCA), that is just as potent as the original compound.

It turns out that dCA inhibits Tat, a protein encoded by the virus. This protein is responsible for amping up viral production. Researchers learned from a study that dCA reduced viral reactivation by 92 percent on average.[1]

The thought, then, is that HIV might be defeated in an opposite fashion from the "shock and kill" approach that many researchers are entertaining. Intense interest has been devoted to finding ways to coerce the virus out of its hiding place so that antiretroviral drugs can defeat it for good. But, if dCA works, it would instead further put on the brakes such that there is minimal viral production or re-expression. Infected cells would be lost to turnover. So, due in no small part to an undersea sponge, HIV, rather than meeting its demise in a final battle, would sail quietly into the sunset.

HemaCare admires the creativity and dedication of scientists working toward an end of HIV. For your HIV research, HemaCare provides blood components and cells from volunteer donors.

Reference

1. Mousseau, G. The Tat inhibitor didehydro-cortistatin A prevents HIV-1 reactivation from latency. 2015. mBio 6(4):e00465-15. doi:10.1128/mBio.00465-15.

Topics: HAART, natural products, Tat, Basic Research

Maria

Written by Maria

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