Up at 5AM: The 5AM Solutions Blog

Potentially, A Key to HIV

Posted on Thu, Feb 19, 2015 @ 03:00 PM

A team of researchers led by Michael Farzan from The Scripps Research Institute in Jupiter, FL may be on the KeystoHIV1cusp of identifying the biggest drug threat to HIV in the 30-year struggle against AIDS. Farzan and his team exploited the AIDS virus' own biomechanics to prevent it from invading healthy white blood cells. 

The drug candidate, called eCD4-lg has the potential to work as both a treatment for patients who already have the virus and as a preventative therapy for at-risk populations. The drug works by, essentially, beating the virus at its own game.

HIV infects healthy white blood cells by docking onto pairs of cellular receptors called CD4 and CCR5. When the virus successfully latches onto the receptors, it works like a key, unlocking the healthy cells, and letting the virus in. Once it's in, the virus makes copies of itself unless those copies are blocked by, for instance, an anti-retroviral drug.

Dr. Farzan and his team of 33 researchers manufactured a molecule that behaves like the virus that causes AIDS. It binds to the cells' receptors, unlocks them, and then makes copies of itself. However, instead of a deadly virus, the drug -- delivered by a harmless virus called an adeno-associated virus (AAV) -- releases copies of itself that bind to the cells and block infection. 

Though this is a potentially exciting development, the drug is still a long way away from clinical use. The researchers tested their therapy on macaque monkeys. Four healthy monkeys were treated with eCD4-lg and were then injected with successively larger doses of SHIV, the simian version of HIV -- far beyond what is necessary to cause an infection.

After 40 weeks, the treated monkeys remained uninfected, and their bodies continued to produce eCD4-lg. Macaques in the control group did not get the drug and all of them contracted HIV.

The NIH-funded study was published online (the full study is available by subscription only) yesterday on the website of the journal Nature ahead of the paper publication.

Image adapted from Keys by Jacqui Brown under CC BY-SA 2.O and HIV  Infected T-Cell by NIAID under CC BY 2.0 both via Flickr.

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Tags: HIV, AIDS, drug development

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