Research finds HIV-killing compound

November 24, 2011

(Medical Xpress) -- A powerful topical preventative for HIV, the virus that causes AIDS, could soon be in the works thanks to a newly discovered molecular compound that research at Texas A&M University and the Scripps Research Institute shows dissolves the virus on contact.

The ability of the synthetic compound known as “PD 404,182” to break apart the AIDS-causing before it can infect cells was discovered by Zhilei Chen, assistant professor in the university’s Artie McFerrin Department of Chemical Engineering, and her team of researchers. Their findings appear in the November online edition of Antimicrobial Agents and Chemotherapy, a journal of the American Society for Microbiology.

“This is a virucidal small-molecule compound, meaning that it has the ability to kill a virus; in this case that virus is ,” Chen says. “Basically, it acts by breaking the virus open. We found that when HIV comes in contact with this compound, it breaks open and loses its genetic material. In a sense, the virus ‘dissolves,’ and its RNA becomes exposed. Since RNA is pretty unstable, once it is exposed it’s gone very quickly and the virus is rendered non-infectious.”

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In other words, the compound works by quickly ripping open the virus before it can inject its genetic material into a human cell. What’s more – and perhaps even more important -– the compound, Chen explains, achieves this by acting on something within the virus other than its viral envelope protein, meaning that the virus can’t alter its proteins to bolster its resistance -– something that’s made HIV notoriously difficult to treat.

“We believe this compound is not working on the viral protein of the viruses but on something else common in all the viruses on which we tested it -- some cellular material common in these viruses,” Chen notes. “Because this compound is acting on a component that is not encoded by the virus, it will be difficult for the virus to evolve resistance against this compound.”

While not a cure for HIV, the compound demonstrates significant potential for use as a preventative, specifically in the form of a topical gel that could be applied in the vaginal canal, Chen explains.

“We conducted a number of tests to demonstrate that this compound remains active in vaginal fluid and is not rendered ineffective,” Chen says. “In the form of a vaginal gel, the compound would serve as a barrier, acting almost instantaneously to destroy the virus before it could infect a cell, thereby preventing HIV transmission from one person to another.”

Surprisingly, Chen and her team did not set out to discover an HIV preventative. Instead, they were conducting screenings of molecules for use in potential drug therapies targeting hepatitis C virus, which causes the dangerous and often fatal disease of the liver. Employing a screening system developed by Chen, the team screened thousands of molecular compounds, in search of those that could block aspects of the HCV life cycle.

During the course of the screenings, the team made an interesting discovery: Not only was PD 404,182 an HCV inhibitor, it also worked on lentiviruses (the group’s negative control in its experimental procedures). Intrigued by that finding, Chen then tested PD 404,182 on HIV, which itself is a lentivirus and found the compound to be even more effective on HIV than on HCV.

“We believe PD 404,182 acts through a unique and important mechanism,” Chen notes. “Most of the known virucidal interact with the virus membrane, but our compound does not appear to interact with the virus membrane. Instead, it bypasses interaction with the membrane and still compromises the structural integrity of the virus.”

The ability of the compound to avoid interaction with the virus membrane is important because human cells have similar membranes, Chen notes. If the compound were to disrupt the structure of the virus membrane, it could also disrupt and ultimately kill human cells. PD 404,182 doesn’t interact with these membranes and is therefore a more attractive option for clinical treatment, Chen says.

As is the case with any potential pharmaceutical, several key steps are still needed before it winds up on drug store shelves. In addition to several rounds of animal studies to ensure the compound is safe for humans, further collaborations with chemists are needed to continue to improve the efficiency of the compound. Chen says. What’s more, Chen also plans to further explore the mechanism by which PD 404,182 breaks apart HIV.

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4.6 / 5 (10) Nov 24, 2011
Thank God for Government funded research.
1.8 / 5 (5) Nov 24, 2011
Vaginal gel? Is that the only possible use of this compound? What about the virus that is already inside the organism? What about prevention of infection from needles, and for other kinds of sex and its other participants? (I'm sure not only the "recipients" will be happy to protect themselves from the virus). Why did they not address these issues at all?
After all, we're not talking about some kind of a marginal discovery here.
5 / 5 (4) Nov 24, 2011
I love science, and @WorldJunkie I'm sure this is the beginning of several possible applications of this discovery. The fact that the virus is being destroyed in a different way is the important part I think, not the fact that it is currently instigated via a gel.
not rated yet Nov 24, 2011
Seems to me it could be something added to the outside of condoms much like a spermicide to prevent HIV infection.
not rated yet Nov 25, 2011
Magic, your live forever med is now here!
not rated yet Nov 28, 2011
Actually, it has been known (published) since the 80s that spermicides - at least those with a detergent like formulas kill the AIDs virus on contact by destroying the viral coating/membrane. That doesn't mean 100% effectiveness, or 100% security. In any case, whether there is sufficient volume of the viricide agent present through out sexual contact and after to maintain safety from dilution by bodily fluids is another critical question and likely one that can't ever likely be guaranteed by any contact agent. The point being - the idea that detergent like compounds denature the viral coating and destroy the virus has been known for some time and certainly not new. One question is how effective the product will be in lowering infection rates - even though it is theoretically never 100% effective. Another question is that in offering a product that is partially effective going to provide a sense of false security, actually raising exposures and infection rates?
1 / 5 (6) Nov 30, 2011
Thank God for Government funded research.

Government funded? By a Texas college and a PRIVATE foundation? Try again.
1 / 5 (6) Nov 30, 2011
Vaginal gel? Is that the only possible use of this compound? What about the virus that is already inside the organism? What about prevention of infection from needles, and for other kinds of sex and its other participants?.. Why did they not address these issues at all?
After all, we're not talking about some kind of a marginal discovery here.

PD 404,182 is not new. It's been in active research for more than a decade. Chen was looking for an agent effective against Hep. C. The HIV connection was serendipitous. This is still very preliminary.

Apparently no one had thought of smearing it on a woman's sexual organs prior to this. Go figure.

Another question is that in offering a product that is partially effective going to provide a sense of false security, actually raising exposures and infection rates?

Another question: is it safe for humans? No word on that yet. Several rounds of safety studies have been proposed.

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