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Medicineworld.org: HIV researchers solve key puzzle

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HIV researchers solve key puzzle




Scientists have made a breakthrough in HIV research that had eluded researchers for over 20 years, potentially leading to better therapys for HIV, as per a research findings published recently in the journal Nature
The researchers, from Imperial College London and Harvard University, have grown a crystal that reveals the structure of an enzyme called integrase, which is found in retroviruses like HIV. When HIV infects someone, it uses integrase to paste a copy of its genetic information into their DNA.



HIV researchers solve key puzzle

Previous to the newly released study, which was funded by the Medical Research Council and the US National Institutes of Health, a number of scientists had tried and failed to work out the three-dimensional structure of integrase bound to viral DNA. New antiretroviral drugs for HIV work by blocking integrase, but researchers did not understand exactly how these drugs were working or how to improve them.

Scientists can only determine the structure of this kind of molecular machinery by obtaining high quality crystals. For the newly released study, scientists grew a crystal using a version of integrase borrowed from a little-known retrovirus called Prototype Foamy Virus (PFV). Based on their knowledge of PFV integrase and its function, they were confident that it was very similar to its HIV counterpart.

Over the course of four years, the scientists carried out over 40,000 trials, out of which they were able to grow just seven kinds of crystals. Only one of these was of sufficient quality to allow determination of the three-dimensional structure.

Dr Peter Cherepanov, the main author of the study from the Department of Medicine at Imperial College London, said: "It is a truly amazing story. When we started out, we knew that the project was very difficult, and that a number of tricks had already been tried and given up by others long ago. Therefore, we went back to square one and started by looking for a better model of HIV integrase, which could be more amenable for crystallization. Despite initially painstakingly slow progress and very a number of failed attempts, we did not give up and our effort was finally rewarded".

After growing the crystals in the lab, the scientists used the giant synchrotron machine at the Diamond Light Source in South Oxfordshire to collect X-ray diffraction data from these crystals, which enabled them to determine the long-sought structure. The scientists then soaked the crystals in solutions of the integrase inhibiting drugs Raltegravir (also known as Isentress) and Elvitegravir and observed for the first time how these antiretroviral drugs bind to and inactivate integrase.

The newly released study shows that retroviral integrase has quite a different structure to that which had been predicted based on earlier research. Availability of the integrase structure means that scientists can begin to fully understand how existing drugs that inhibit integrase are working, how they might be improved, and how to stop HIV developing resistance to them.


Posted by: Mark    Source




Did you know?
Scientists have made a breakthrough in HIV research that had eluded researchers for over 20 years, potentially leading to better therapys for HIV, as per a research findings published recently in the journal Nature The researchers, from Imperial College London and Harvard University, have grown a crystal that reveals the structure of an enzyme called integrase, which is found in retroviruses like HIV. When HIV infects someone, it uses integrase to paste a copy of its genetic information into their DNA.

Medicineworld.org: HIV researchers solve key puzzle

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