Exploiting the methylerythritol phosphate pathway as a source of drug targets for novel anti-infectives

Anti-infective resistance is a serious global healthcare issue, calling for the development of compounds with a novel mode of action. An interdisciplinary approach will afford potent and selective inhibitors of the underexplored methylerythritol phosphate pathway, a rich source of targets that are essential for medically relevant pathogens such as the causative agents of malaria and tuberculosis. The discovery of anti-infective agents requires a highly interdisciplinary approach. A lack of a coherent training on the fundamental aspects and design principles encompassing all relevant disciplines delays the discovery and optimisation of urgently needed candidates for commercial development. This network aims to train the next generation of scientists with cutting-edge interdisciplinary skills in the discovery of new anti-infective agents through a an innovative training programme, setting the stage for the discovery of urgently needed anti-infectives with an unprecedented mechanism of action, as a springboard for translational research and industrial applications. There is a natural progression in both the training and research programme from (i) structural biology of the target enzymes, via (ii) the design and synthesis of inhibitors to (iii) fragment screening as well as multiparameter optimisation including cell-based testing and profiling with chemical proteomics. This network unites leading experts with complementary expertise in anti-infective agents from across Europe and comprises 17 partners in total: 11 academic partners and 6 non-academic partners from 8 countries, including 3 SMEs (1 designing screening libraries, 1 using chemical proteomics for target identification/deconvolution and the study of resistance formation and 1 developing bioinformatics tools for drug discovery), 1 large pharmaceutical company and 2 charities focussing on neglected diseases and promoting science to the general audience.