BSC and IrsiCaixa create a computational method to predict the effectiveness of antiretroviral drugs
The Barcelona Supercomputing Center – BSC and IrsiCaixa (the Catalan AIDS Research Institute), have developed a bioinformatics method to predict the effect of mutations on the resistance the HIV and other retroviruses to specific drugs.
See the work published in the Journal of Chemical Information and Modeling by Ali Hosseini, Andreu Alibés, Marc Noguera-Julian, Victor Gil, Roger Paredes, Robert Soliva, Modesto Orozco, and Victor Guallar.
In this study we demonstrate how to connect routine clinical diagnosis of HIV-1 with structural computer modelling. This is a multidisciplinary proof of concept which overcomes the limitations of current practice when deciding antiretroviral treatment and which, in addition, allows new drugs to be designed more quickly (says Marc Noguera-Julian, IrsiCaixa, co-author of the study).
The effectiveness of antiretroviral drugs used to treat HIV (human immunodeficiency virus) is frequently affected by the virus ability to develop genetic mutations. The BSC-IrsiCaixa method predicts the effect of each mutation on the resistance of the virus to such drugs. The method combines HIV DNA sequencing, identification of genetic mutations, computational protein modelling and the simulation of drugs binding with the proteins of the virus. The entire bioinformatics analysis can be performed in fewer than 24 hours on relatively small-scale computing equipment available to any laboratory.
One of the main features of the strategy is the use of PELE, a software developed at BSC to predict how drugs will interact with their targets, which has been shown to have competitive advantages over commercially available software. BSC has created an automatic platform, available for free via the web, on which researchers can enter a patient’s HIV-1 PR protease genomic sequence and predict the effectiveness of prescribing the drugs amprenavir and darunavir. For the moment, these are the only predictions available, pending advances in research on the effect of HIV mutations on other proteins within the virus and interactions with other antiretroviral drugs.
BSC researcher Victor Guallar, PI of the study and lead developer of PELE, explains that
this system is one of the first tangible steps in the area of what will eventually be personalised medicine, where treatment will be decided following genetic analysis of the causes of the disease in each patient and of which drug would be most effective in each individual case.
