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

July 8, 2011

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

Paris spotlight on latest in AIDS science

July 21, 2017
Some 6,000 HIV experts gather in Paris from Sunday to report advances in AIDS science as fading hopes of finding a cure push research into new fields.

Scientists elicit broadly neutralizing antibodies to HIV in calves

July 20, 2017
Scientists supported by the National Institutes of Health have achieved a significant step forward, eliciting broadly neutralizing antibodies (bNAbs) to HIV by immunizing calves. The findings offer insights for HIV vaccine ...

Heart toxin reveals new insights into HIV-1 integration in T cell genome

July 20, 2017
Human immunodeficiency virus (HIV)-1 may have evolved to integrate its genetic material into certain immune-cell-activating genes in humans, according to new research published in PLOS Pathogens.

Scientists capture first high-resolution image of key HIV protein transitional state

July 13, 2017
A new, three-dimensional snapshot of HIV demonstrates the radical structural transformations that enable the virus to recognize and infect host cells, according to a new study led by scientists at The Scripps Research Institute ...

Barrier to autoimmune disease may open door to HIV, study suggests

July 11, 2017
Researchers from the University of Colorado School of Medicine have discovered that a process that protects the body from autoimmune disease also prevents the immune system from generating antibodies that can neutralize the ...

Team tests best delivery mode for potential HIV vaccine

June 20, 2017
For decades, HIV has successfully evaded all efforts to create an effective vaccine but researchers at The Scripps Research Institute (TSRI) and the La Jolla Institute for Allergy and Immunology (LJI) are steadily inching ...

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.