Drug designer: New tool reveals mutations that cause HIV-drug resistance

July 8, 2011, National Institute for Mathematical and Biological Synthesis

Protease inhibitor drugs are one of the major weapons in the fight against HIV, the virus that causes AIDS, but their effectiveness is limited as the virus mutates and develops resistance to the drugs over time. Now a new tool has been developed to help predict the location of the mutations that lead to drug resistance.

First discovered in 1995, protease inhibitor drugs have dramatically reduced the number of AIDS deaths. Taken in combination with two other anti-HIV drugs, protease inhibitors work by halting the action of the protease enzyme, a protein produced by HIV that is necessary for replication of the virus. However, almost half of who initially respond to treatment with protease inhibitors develop strains and stop responding to treatment within eight to 10 months.

Currently there are nine FDA approved protease inhibitors, and 21 most common drug-resistant mutations.

The main reason for the short-term effectiveness of the drug has to do with the evolution of the drug within the body, said the study's author, Yi Mao, a postdoctoral fellow at the National Institute for Mathematical and .

In the new study, published today in the journal BMC Structural Biology, Mao used a mathematical modeling technique called elastic network modeling to examine the physical properties and interactions of the proteins. The model reveals where mutations are occurring during the evolution of the proteins and how these mutations help the virus survive.

"With this kind of knowledge, better strategies for designing anti-HIV drugs could be developed," Mao said.

HIV kills the body's , called CD4 cells. Once the number of CD4 cells dips below 200, an HIV patient enters the last stage of his or her disease: Acquired Immune Deficiency Syndrome, or AIDS. The first cases of AIDS were reported thirty years ago. Since then, more than 60 million people have been infected with HIV, and more than 30 million people have died from AIDS. Today an estimated 34 million people worldwide are living with HIV – 1.2 million in the U.S.

More information: Mao Y. 2011. Dynamical Basis for Drug Resistance of HIV-1 Protease. BMC Structural Biology. Published online 8 July 2011. 11:31. doi:10.1186/1472-6807-11-31

Related Stories

Recommended for you

HIV-1 genetic diversity is higher in vaginal tract than in blood during early infection

January 18, 2018
A first-of-its-kind study has found that the genetic diversity of human immunodeficiency virus type 1 (HIV-1) is higher in the vaginal tract than in the blood stream during early infection. This finding, published in PLOS ...

War in Ukraine has escalated HIV spread in the country: study

January 15, 2018
Conflict in Ukraine has increased the risk of HIV outbreaks throughout the country as displaced HIV-infected people move from war-affected regions to areas with higher risk of transmission, according to analysis by scientists.

Researchers offer new model for uncovering true HIV mortality rates in Zambia

January 12, 2018
A new study that seeks to better ascertain HIV mortality rates in Zambia could provide a model for improved national and regional surveillance approaches, and ultimately, more effective HIV treatment strategies.

New drug capsule may allow weekly HIV treatment

January 9, 2018
Researchers at MIT and Brigham and Women's Hospital have developed a capsule that can deliver a week's worth of HIV drugs in a single dose. This advance could make it much easier for patients to adhere to the strict schedule ...

New long-acting, less-toxic HIV drug suppresses virus in humanized mice

January 8, 2018
A team of Yale researchers tested a new chemical compound that suppresses HIV, protects immune cells, and remains effective for weeks with a single dose. In animal experiments, the compound proved to be a promising new candidate ...

Usage remains low for pill that can prevent HIV infection

January 8, 2018
From gritty neighborhoods in New York and Los Angeles to clinics in Kenya and Brazil, health workers are trying to popularize a pill that has proven highly effective in preventing HIV but which—in their view—remains woefully ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.