Projetos e áreas de actuação

PROJECTS

Non-structural protein 5 (NS5) as target for anti-zika compounds

The Zika virus (ZIKV) is a flavivirus that came into evidence only in 2015, when the last outbreak occurred after six decades, starting in Brazil and spreading to several countries in the Americas. This virus achieved notoriety mainly due to its ability to cross the human placental barrier, causing congenital malformations, especially microcephaly.

Based on the known ZIKV mutations, as well as in comparisons with other flaviviruses, our group suggested NS5 as the most interesting target for the development of novel anti-ZIKV compounds. Currently, our group works on the study of the protein dynamics, and the search, by means of Virtual Screening, of new compounds targeting the RpRd domain.

This work is a performed in collaboration with Dr. Paulo Ricardo Batista, PROCC/Fiocruz.

Molecular characterization of BK polyomavirus in renal transplanted patients

Polyomavirus BK (BKPyV) is an emerging opportunistic infection agent among renal transplant patients, which may undergo reactivation progressing to nephropathy and consequent graft loss in up to 10% of renal transplants. In addition, in the last two years, several publications have observed the presence of BKPyV in malignant prostate tumors. There are currently no specific treatments for BKPyV infections, and the reduction of immunosuppression is the only available palliative measure. Our group works in the search, using Virtual Screening (VS) methods, of anti-BKPyV drugs, targeting the proteins Lt-ag (major tumor antigen), a multifunctional protein of all polyomaviruses, and VP-1 (viral protein 1), the main constituent of the viral capsid, and responsible for the recognition of cellular receptors.

This project is performed in collaboration with Prof. Rafael Varella Brandao, from the Universidade Federal Fluminense (UFF), who is responsible for testing the compound ability to inhibit viral replication.

Development of new anti-chagas agents

Chagas disease, or American trypanosomiasis, is an infection caused by the protozoan parasite Trypanosoma cruzi. This disease is a major public health problem and a major cause of morbidity, long-term disability, and mortality in Latin America. The available therapies have a high rate of adverse effects. Thus, there is an urgent need for the development of novel anti-Chagas compounds.

The group of Prof. Silvia Pérez-Silanes, from the University de Navarra (UNAV), Pamplona, Spain, is working in the search of new anti-chagas agents targeting the Superoxide Dismutase (SOD) enzymes. Docking studies are helping in understanding structure-activity relationships of the novel compounds, so as in the rational design of new series.

Structural and functional characterization of proteins involved in cancer development

The knowledge of all the genes/proteins involved in regulating the integrity of the cell cycle is the main focus of the studies in the field of cancer. However, many of these genes and their proteins are still neglected, and in some cases we have yet no clue about their function. As part of a worldwide effort in the search for anti-cancer therapy, Prof. Marcius da Silva Almeida, from the Institute of Medical Biochemistry ( IBqM ) of the UFRJ, is focused on the functional and structural determination of Glucose-induced degradation protein 8 homolog (Gid8), which belongs to the CTLH ubiquitination complex, and in Bex3 protein, involved in apoptosis mediated by p75NTR.

Because of the existence of intrinsically unstructured and coiled-coil regions in these proteins, the structural determination by common experimental methods is highly complicated, and new approaches combining computational techniques are being applied.

Structural analysis and biotechnological applications of pore forming toxins

Pore-forming toxins (PFTs) are the most common bacterial cytotoxic proteins. They are produced as soluble monomers that subsequently oligomerize and convert to a pore in the target membrane, leading to the destruction of its permeability barrier and subsequently to osmotic lysis. These proteins are not exclusive to bacteria, but they are produced by a variety of organisms, and are often involved in defense or attack mechanisms. Apart from its virulence characteristics, they are interesting for its potential as bio technological sensors and delivery systems.

In a project coordinated by Prof. Matteo dal Peraro, from the École Polytechnique Fédérale de Lausanne, we are studying the structure and dynamics of the aerolysin subfafily of PFTs. In the last years, our efforts have been focused on the use of this protein, so as of rationally designed mutants, for molecular sensing.