iCHEMGENODRUGS_TB · Chemogenomics and in silico repurposing as an innovative approach for rapid drug discovery in tuberculosis
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2018-09-01 → 2020-08-31
- EU contribution
- €148,636
- Participants
- 1
- Scheme
- MSCA-IF-EF-CAR
Lines connect the coordinator with its partners.
Results in brief
Chemogenomics and in silico repurposing as an innovative approach for rapid drug discovery in tuberculosis
Tuberculosis (TB) remains a serious Public Health problem in many countries, causing millions of deaths per year. The World Health Organization launched the “End TB” strategy, which aims to reduce TB deaths by 95% and to cut new cases by 90% between 2015 and 2035. Although there has been a decrease in global TB incidence rates and mortality, the present rate of such decline is insufficient to meet the 2035 goals. Treatment of multidrug resistant TB (MDRTB) is extremely difficult since it requires more expensive drugs with a higher toxicity profile, during a longer period (up to 24 months), resulting in patient non-compliance and poorer outcomes. Therefore, there is a need to identify new drugs and new combined therapies that are better tolerated with the possibility to treat both drug-susceptible and drug-resistant TB alike, more quickly and efficiently. In general, conventional drug discovery strategies are usually costly and time-consuming and, frequently, with low success rates. An alternative approach to accelerate and cheapen drug discovery is to find new uses for existing approved drugs, a practice known as drug repurposing. Since a repurposed drug does not trail through the research phase, it can follow directly to preclinical testing and clinical trials, thus reducing time, costs and risk. This project used drug repurposing combined with comparative chemogenomics to identify drugs that target proteins involved in energy metabolism and membrane transport of Mycobacterium tuberculosis. This strategy identified 18 potential M. tuberculosis targets and 23 approved drugs. A group of selected compounds was evaluated using different in vitro methodologies, in order to identify the most promising drugs. This project contributed to the development of a new paradigm for the design of new drugs and new therapeutic strategies to be used in the fight against TB.
Data: CORDIS, © European Union
Project objective
Tuberculosis is one of the most worrying Global and Public Health problems in the present day and causes a major economic and social burden, which can significantly drain a society’s resources. In 2015, 10.4 million people fell ill with tuberculosis and 1.8 million died from the disease. In addition, an estimated 480000 people developed multidrug-resistant tuberculosis. The development of new drugs and new therapeutic regimens effective against drug susceptible and drug resistant tuberculosis is one of the greatest challenges in the way of tuberculosis control. Conventional drug discovery strategies are usually costly and time-consuming and, frequently, with low rates of success. This project aims to develop a new paradigm for tuberculosis drug development, using the drug repurposing strategy (to find new uses for already approved drugs) coupled with an in silico chemogenomics method. The focus will be targeting energy metabolism, particularly the oxidative phosphorylation, a novel target pathway in tuberculosis drug discovery. This research project has the potential to greatly benefit tuberculosis drug discovery by finding new drugs for a largely unexplored pathway and by introducing a new approach that can increase the probability of identifying effective drugs and decrease the bottlenecks of the conventional drug discovery approach, saving both time and money. Since tuberculosis has a high social and economic impact, this project aims not only to contribute to scientific and academic knowledge in this field, but also to increase public awareness on tuberculosis drug resistance and the need for new drugs by using several outreach activities. Finally, searching for new effective drugs that can tackle the problem of drug resistance and reduce the costs of drug treatment contributes to the decrease of social impact and economic burden of this disease and is in line with the goals of the World Health Organization “End TB” strategy.
Original text from CORDIS.
Participants
- UNIVERSIDADE NOVA DE LISBOA · LisboaCoordinatorPortugal
Links
- View on CORDIS
- DOI: 10.3030/795924
- https://ghtm.ihmt.unl.pt/research/research-groups/tb-hiv-opportunistic-diseases-pathogens-thop/
Data: CORDIS, © European Union