Metal-Containing Compounds Show Promise as HIV Weapon
The molecule – called metallicacarborane – and its variants appear to fight HIV protease, an enzyme critical in the virus’ life cycle.
“This molecule has all the characteristics of a good starting point for a new class of compounds,” said Dr. Zbyszek Otwinoski, associate professor of biochemistry at UT Southwestern and an author on the study, which appears in the Proceedings of the National Academy of Sciences.
Researchers from UT Southwestern, the Czech Republic, and Germany studied the structure and inhibition properties of the basic molecule as well as several variants with chains of other atoms hanging off them.
The 12-pointed, cagelike molecule of boron bound to carbon, called carborane, has been known for more than 50 years but just recently came to the attention of researchers in the Czech Republic as a possible AIDS (Acquired Immune Deficiency Syndrome) drugs, Dr. Otwinowski said.
The Czech group bound the metallicacarboranes they were studying to the proteases, then brought the defraction data to UT Southwestern to have the structures interpreted.
The metallicacarboranes appeared to occupy the portion of the protease used to hold key proteins in place as part of the infective cycle of HIV, preventing the proteases from working.
Other advantages are that the compounds are stable and can be modified in many ways be attaching strings of atoms to them.
These compounds were also found to bind to the protease in a different location than the current class of protease inhibitors, so they may be effective against HIV strains that have become resistant to that class.
Dr. Pavlina Rezacova, postdoctoral researcher in biochemistry at UT Southwestern, also participated in the study, as did researchers from the Academy of Sciences of the Czech Republic, the Institute of Chemical Technology, Charles University in the Czech Republic, and the University of Heidelberg in Germany.
The work was supported in part by the European Commission and the Ministry of Education of the Czech Republic.
Drug resistance is the biggest reason HIV drugs stop working and three out of four people taking HIV drugs have drug resistance.
One out of four people with HIV who have never taken HIV drugs already have drug resistance according to an HIV website.
Taking HIV drugs on time every day can help fight drug resistance and a resistance test can help doctors pick better drugs for people living with HIV.
