( A computational model has been develope...)Computational Model Reveals Working of AZT in Body,Health

A computational model has been developed by researchers at the Virginia Bioinformatics Institute (VBI) at Virginia Tech which would allow scientists to have a better //understanding of the metabolism and toxicity of the HIV/AIDS drug zidovudine (azidothymidine, AZT).

AZT is used successfully as part of Highly Active Anti-Retroviral Therapy (HAART) to control the level of the human immunodeficiency virus in HIV-infected individuals. However, long-term use of AZT may lead to side-effects in some patients. David Samuels and coworkers are interested in finding out whether the toxic side effects of AZT can eventually be minimized or even eliminated. For this purpose, they have been developing a detailed computational model that allows scientists to simulate the biochemical reactions that take place when AZT is metabolized in cells, including their mitochondria, under different metabolic conditions. Drugs like AZT may interfere with DNA replication in the mitochondria, the energy factories of our cells, and can lead to potentially fatal side effects in patients undergoing HAART treatment.

Samuels, assistant professor at VBI, commented: "HAART is one of the biggest success stories in modern medicine. The goal of our work is to help improve this successful treatment by understanding the toxic effects that AZT can have in some people. There are many different ways that AZT could possibly interfere with mitochondria to cause the toxic side-effects. Our job is to model these proposed toxicity mechanisms to see which ones could actually lead to the mitochondrial defects found in AIDS patients." He added: "It is possible that no single mechanism is responsible for the toxicity, but that instead a combination of multiple effects is needed. That is the kind of problem that needs a systems biology approach."

When AZT reaches a cell, it is subject to some of the same metabolic modifications or phosphorylation events that are encountered by the four natu
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