Breakthrough in HIV research
9 Mar 2010 by Evoluted New Media
Scientists have made a major breakthrough in HIV research after finding the answer to a 20 year-old puzzle – the three-dimensional structure of an enzyme found in the retrovirus.
Scientists have made a major breakthrough in HIV research after finding the answer to a 20 year-old puzzle – the three-dimensional structure of an enzyme found in the retrovirus.
Many have tried and failed to work out the structure of integrase – an enzyme which pastes a copy of its genetic information into host DNA upon infection. Current antiretroviral drugs for HIV block integrase, but scientists didn’t understand how they were working or how to improve them.
Scientists from Imperial College London and Harvard University grew crystals of the enzyme and examined its structure when bound to viral DNA – work which could lead to better treatments for the disease.
“It is a truly amazing story. When we started out, we knew the project was very difficult,” said Dr Peter Cherepanov, lead author from the Department of Medicine at Imperial, “We went back to square one and started looking for a better model of HIV integrase, which could be more amenable for crystallisation.”
Researchers grew a version of integrase borrowed from a little-known retrovirus called Prototype Foamy Virus (PFV). Over four years, they carried out 40,000 trials and we able to grow just seven kinds of crystal – only one of which was of sufficient quality to allow determination of the 3D structure.
The giant synchrotron machine at Diamond Light Source in South Oxfordshire was used to collect x-ray diffraction data from the crystal, which enabled researchers to determine its structure. The crystals were then soaked in integrase-inhibiting drugs Ralegravir and Elviregravir, and researchers were able to observe how the drugs bound to and inactivated integrase.
“Despite initially painstakingly slow progress and many failed attempts, we did not give up and our effort was finally rewarded,” Cherepanov said.
