Defence peptide forms basis for new HIV drug

Modern combinations of antiretroviral therapies have been used successfully to treat many people with HIV. However, concern is growing that new medications will be required as the virus mutates to render current drugs ineffective.

The HIV-1 virus often mutates quickly to overcome antiviral compounds designed to prevent infections. But the researchers demonstrated that over the course of 100 days the virus developed a weak resistance to retrocyclin, a defence peptide still found in monkeys and lower primates.

Lead researcher, Professor Alexander Cole of UCF's Burnett College of Biomedical Sciences said that if additional laboratory tests could demonstrate only weak resistance, the next step would be to study how retrocyclin could be developed into a drug designed to prevent the HIV virus from entering human cells.

There are three classes of defensin peptides, and most research has focused on alpha and beta defensins, the two types that humans still make.

However, previous studies have demonstrated that theta-defensins are more active against HIV-1 than the other two types of defensins and can be developed in laboratories.

Cole is now working to develop a way to grow retrocyclin through genetically engineered tobacco plants.

The retrocyclin gene would be incorporated into the chloroplast genome of tobacco cells before the plants grow. A similar approach has been developed to grow anthrax vaccine in tobacco plants.

An inexpensive way to produce the drug with only a small amount of tobacco would help to make it accessible in areas such as Southeast Asia, Africa and the Caribbean where the disease spreads most quickly.

"If we could develop retrocyclin in plants and produce enough of the drug cheaply, we could potentially save a lot of lives,"​ Cole said.

At the end of 2005 there were an estimated 40.3m people living with HIV worldwide. There were 4.9m new HIV infections in 2005 and 3.1m AIDS-related deaths.

HIV-1 is the most common form of the human immunodeficiency virus that causes AIDS.

The disease is often transmitted sexually, and the drugs produced from Cole's research would be applied to the vagina in the form of a gel or cream.

Many of the laboratory tests have shown that retrocyclin can prevent HIV-1 infection of human vaginal tissue.

Retrocyclin was still an effective inhibitor of HIV-1 even after 100 days of continuous exposure to human cells in a laboratory setting.

The exact reason why resistance does not develop quickly with retrocyclin is unclear, but it may be a result of retrocyclin interacting with more than one target on both the cell and virus.

Viruses that have to defeat more than one antiviral mechanism often develop resistance at a much slower pace.

The next phase of Cole's research will delve more into the mutations that HIV-1 can take in an effort to minimise them as much as possible. Many series of laboratory tests would need to be completed before clinical trials could begin no earlier than 2009.

The findings were published in the June 1 issue of The Journal of Immunology.