Scientists say crack HIV/AIDS puzzle for drugs

Sun Jan 31, 2010 1:00pm EST

* Study solves puzzle that eluded scientists for 20 years

* Finding should help development of new HIV/AIDS medicines

* Allows scientists to see how Merck and Gilead drugs work

By Kate Kelland

LONDON, Jan 31 (Reuters) - Scientists say they have solved a crucial puzzle about the AIDS virus after 20 years of research and that their findings could lead to better treatments for HIV.

British and U.S. researchers said they had grown a crystal that enabled them to see the structure of an enzyme called integrase, which is found in retroviruses like HIV and is a target for some of the newest HIV medicines.

"Despite initially painstakingly slow progress and very many failed attempts, we did not give up and our effort was finally rewarded," said Peter Cherepanov of Imperial College London, who conducted the research with scientists from Harvard University.

The Imperial and Harvard scientists said that having the integrase structure means researchers can begin fully to understand how integrase inhibitor drugs work, how they might be improved, and how to stop HIV developing resistance to them.

When the human immunodeficiency virus (HIV) infects someone, it uses the integrase enzyme to paste a copy of its genetic information into their DNA, Cherepanov explained in the study published in the Nature journal on Sunday.

Some new drugs for HIV -- like Isentress from Merck & Co (MRK.N) and elvitegravir, an experimental drug from Gilead Sciences (GILD.O) -- work by blocking integrase, but scientists are not clear exactly how they work or how to improve them.

The only way to find out was to obtain high-quality crystals -- a project that had defeated scientists for many years.

"When we started out, we knew that the project was very difficult, and that many tricks had already been tried and given up by others long ago," said Cherepanov.

"Therefore, we went back to square one and started by looking for a better model of HIV integrase which could be more amenable for crystallisation."

The researchers grew a crystal using a version of integrase borrowed from another retrovirus very similar to its HIV counterpart.

It took more than 40,000 trials for them to come up with one a crystal of sufficiently high quality to allow them to see the three-dimensional structure, they said.

They tested the Merck and Gilead drugs on the crystals, and were able to see for the first time how the medicines bind to, and block, integrase.

Almost 60 million people have been infected with HIV and 25 million people have died of HIV-related causes since the beginning of the AIDS epidemic. There is no cure and no vaccine, although drug cocktails can keep patients healthy.

United Nations data for 2008 show that 33.4 million people had HIV and 2 million people died of AIDS. The worst-affected region is sub-Saharan Africa, accounting for 67 percent of all people living with HIV.

(Editing by Michael Roddy)

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Comments (23)
What does this story have to do with Cancer?

Jan 31, 2010 2:01pm EST  --  Report as abuse
“Interruption”. Interesting that you find someone with the Aids/HIV death sentence an Interruption to life. What a shame your narrow minded bigotry is focused alone on one disease, albeit a terrible one. More than likely someone close to you already has HIV, but has yet to be diagnosed or revealed it to you. Without proper research into this devestating destruction of humanity, it is obvious to so many that this virus will spread faster and further into the small world you inhabit. I wonder. I wonder when people with your mentality will understand and realize that HIV/Aids is not an African or Homosexual issue alone, but a global epidemic of monsterous proportions and significantly will impact all if not contained and a cure found. I do wonder.

Jan 31, 2010 2:06pm EST  --  Report as abuse
Neplusultra wrote:
Exactly, after how many billions and billions spent on a 100% avoidable disease. This is exactly what you can expect if the government takes over healthcare. Research driven by political pressure instead of actual need.

Jan 31, 2010 2:08pm EST  --  Report as abuse
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