Research Institute for Medicines (iMed.ULisboa)/ Faculty of Pharmacy, University of Lisbon (FFULisboa)
Member of the Executive Board, iMed.ULisboa
Director of the Drug Design Division, iMed.ULisboa
Full Professor, Pharmaceutical and Medicinal Chemistry, FFULisboa
Research Institute for Medicines (iMed.ULisboa)
Faculty of Pharmacy, University of Lisbon
Av. Prof. Gama Pinto
Rui Moreira is a professor of pharmaceutical and medicinal chemistry at the Faculty of Pharmacy, University of Lisbon (FFULisboa) and Director of the Drug Design Division (DDD) at the Research Institute for Medicines (iMed.ULisboa), managing a team of 50 scientists. DDD is a chemistry-centered platform oriented to the discovery of biologically active chemical entities with the ultimate goal of optimizing their therapeutic properties and value. To attain this goal, DDD groups make use of a wide-range of technologies and strategies including in silico and biochemical-based screening of focused chemical libraries, fragment- and structure-based design of ligands, bio-guided fractionation of plant extracts, synthetic organic chemistry and development of bioconjugates.
Rui Moreira has a long-stand interest in the design of antimalarials, in particular novel chemical approaches to address the lack of drugs active against the liver and sexual blood stages of malaria parasites, which remain underexploited targets for prophylaxis and disease elimination. Complementarily, Rui Moreira is also involved in developing in silico approaches to design or identify novel anti-infectious drugs, including protocols for the virtual screening of chemical libraries against targets of pathogens, such as the mitochondrial electron transport system of Mycobacterium tuberculosis and parasites, as well as key proteins associated to HIV invasion process. Natural products are also at the core of Moreira’s interest due to their structural diversity and molecular complexity, key structural features to generate novel chemotypes with potential for modulating novel targets. In this context, Moreira’s group designed, synthesized and evaluated natural products-based libraries as antiparasitic agents. Recently, Rui Moreira initiated a program focused in developing chemical probes for activity- and photoaffinity-based protein profiling and target identification, leading several research projects in this field, funded by the Portuguese Foundation for Science and Technology, towards the identification of novel targets in infectious diseases using chemical proteomics. Additional information can be found at Researcher ID G-7485-2011 and ORCID ID 0000-0003-0727-9852.
The Research Institute for Medicines (iMed.ULisboa) is the R&D Unit of the Faculty of Pharmacy, University of Lisbon (FFULisboa) for pharmaceutical research that strives for new discoveries to improve human health through prevention, diagnosis and treatment. Our translational research spans the spectrum of drug discovery, design, development and usage in human diseases, such as cancer and neurodegenerative, metabolic and infectious disorders. iMed.ULisboa is a large R&D Unit hosting 200 scientists, and is a driving force behind drug discovery and development efforts in Portugal, and an attractive partner at a global level that thrives for major gains in medical and health sciences, research and training
FFULisboa/iMed.ULisboa is committed to spin innovative research on pathogen evolution to other forms of virulence and drug resistance, and develop molecular strategies to control microbial infection. Part of our bacteriophage research and antibody discovery has been developed in collaboration with biotechs (TreatU, TechnoPhage). Moreover, we collaborate with institutions worldwide in molecular epidemiology and genome-wide analysis of multi- and extensively drug-resistant M. tuberculosis. We have identified genetic determinants of drug resistance, including new mutations and interactions between drug resistance-associated genes, which highlight the role of efflux pumps and provide hints to rapid molecular diagnosis. We are often involved in assessment of trends in health, providing global and national estimates on infection to improve control measures and inform patient management. Finally, iMed.ULisboa scientists have developed a novel and potent fusion inhibitor of HIV infection based on a rational strategy for synthetic antibody library construction. Engineered transcriptional modulators based on customizable transcription activator-like effector (TALE) proteins can induce gene expression from the HIV-1 long terminal repeat promoter, and combinations of TALE transcription factors can synergistically reactivate latent viral expression in cell line models of HIV-1 latency. The Drug Design Division (DDD) at iMed.ULisboa is involved in projects related to the discovery of novel antibiotics and antiviral agents.
Rui Moreira and iMed.ULisboa/FFULisboa can provide expertise in medicinal chemistry, organic synthetic chemistry, chemical biology and natural products chemistry within the consortium. In particular, the following topics can be highlighted:
Development of bio-inspired, efficient and sustainable synthetic methodologies for the preparation of small molecule modulators of enzymes and proteins; development of general synthetic methods to modify a broad range of proteins and use them in the synthesis of therapeutically useful bioconjugates and chemical probes.
Design of focused chemical libraries that can generate robust starting points from target- and phenotypic whole cell-based screening campaigns. Currently, we have a unique library of ca. 1000 compounds (including natural products) with a wide range of structural motifs that will be screened within the context of the consortium.
Computational discovery of chemical probes by developing technically advanced computer-aided drug refinement tools to streamline the hit generation process for targets emerging from biology groups. We are also aiming at unfolding potential multitargeting for validated lead compounds or drug candidates as a tool to overcome drug resistance.
Development of prodrug strategies to increase the selectivity of lead compounds or drug candidates towards their intended targets by designing derivatives that are preferentially activated by cell-specific enzymes.
Importantly, the required biology support is also available at iMed.ULisboa, including a screening facility, P3 laboratory. In addition, a mass spectrometry facility for drug metabolism is also fully available for drug discovery projects.