CNPEM research, supported by Finep, reveals new pathway for Chagas disease treatments

Studies carried out at Sirius reveal a new therapeutic target for the development of drugs against Trypanosoma cruzi

 

Research conducted by CNPEM (Brazilian Center for Research in Energy and Materials), in Campinas (SP), funded by Finep (Brazilian Funding Authority for Studies and Projects), linked to the Ministry of Science, Technology and Innovation (MCTI), has opened a new front for developing treatments for Chagas disease, which is chronic in Brazil. Scientists have identified a molecule effective against Trypanosoma cruzi and elucidated its mechanism of action using Sirius facilities, the Brazilian synchrotron light source. The results were published in the Journal of Medicinal Chemistry, a highly prestigious journal in the field of medicinal chemistry and drug discovery.

This work is the result of research that began about a decade ago at CNPEM, a social organization funded by MCTI, and which, in recent years, with support from Finep, has advanced to the preclinical study phase. The discovery gains relevance given the scale and social impact of the disease in the country.

“This project demonstrates, in practice, the importance of Finep supporting scientific and technological research in strategic areas for the country. These are long-term, complex initiatives that involve high technological risk and have significant potential to generate knowledge and solutions with enormous impact on society. By contributing to the advancement of an investigation conducted at CNPEM from basic research to preclinical studies, Finep strengthens Brazil’s capacity to develop new therapeutic alternatives for a disease that still represents a significant public health challenge”, says Joana Meirelles, Superintendent of Health at Finep.

The Ministry of Health believes that there may be around 4.6 million people infected with Trypanosoma cruzi, the vast majority of whom asymptomatic and not yet diagnosed (data from the Brazilian Federal Government). A study published in 2025 by The Lancet, on the economic impacts of Chagas disease in Latin American countries, estimated the impact on Brazil at US$11.4 billion annually, equivalent to 0.23% of GDP. These numbers reinforce the need to advance research into new treatments for people affected by the disease.

In the scientific article, the researchers reveal, at the atomic level, the three-dimensional structure of the complex established between the drug candidate molecule and its respective molecular target, an enzyme called Lysyl-tRNA Synthetase, or simply KRS.

“The major difficulty in developing new drugs against Chagas disease is that we still know relatively little about the essential mechanisms for the parasite’s survival. The main result of this work is the validation of a new target and a new mechanism of action that can now be

explored in drug development”, says Artur Torres Cordeiro, researcher at CNPEM and one of the coordinators of the study.

Tests with the KRS inhibitor in live models infected by T. cruzi were conducted by veterinarian Thais Cristina Dos Santos, first author of the article. The experiments mimicked the early stage of the disease, when the parasite can be detected in large quantities in the bloodstream and inside the cells of the heart and intestines.

The KRS inhibitor was administered orally for ten days. From the third day of treatment onwards, the parasite could not be detected in the animals’ blood—a result that persisted throughout the evaluation period. The treatment also significantly reduced the parasite load found in the heart, spleen, and colon, compared to untreated infected animals. The observed effect was comparable to that of benznidazole, the reference drug for Chagas disease. Although effective in the acute phase, benznidazole shows limited efficacy when the disease progresses to the chronic phase.

The next steps consist of evaluating the efficacy of the KRS inhibitor in the chronic stage of Chagas disease and in a second clinical model. If successful, the molecule could proceed to human trials. Researchers emphasize that the molecule is still in the testing phase and is not a medication available for patients.

The research stems from basic and multidisciplinary investigation at the interface between physics, chemistry, and biology. Throughout this path, the research group analyzes different proteins from T. cruzi to identify potential therapeutic targets that neutralize its pathogenic effects — a complex, costly, and long-term task. In addition to MCTI, the project received support from CNPq, FAPESP and FINEP, whose recent support allowed the hiring of specialists in organic chemistry and veterinary medicine. Also noteworthy are the collaborations of researchers from Unicamp and the Federal University of Goiás.

“We are using our state-of-the-art facilities to help solve a problem that affects the most underserved in our population. Most people don’t realize it, but this is one of the ways we give back to society the investment made in science and technology”, says Cordeiro.

According to Finep’s Health Superintendent, Joana Meirelles, Finep’s encouragement of research demonstrates the importance of the agency in the search for solutions that significantly impact the population’s quality of life. “This project demonstrates, in practice, the importance of Finep supporting scientific and technological research in strategic areas for the country. This is long-term, complex research that involves risks, but can generate knowledge and solutions that have a huge impact on society. By contributing to the advancement of research conducted at CNPEM from basic research to preclinical studies, Finep strengthens Brazil’s capacity to develop new therapeutic alternatives for a disease that still represents a significant public health challenge.”

Sirius helped reveal how the molecule works

A decisive stage of the study was carried out at the Manacá beamline of Sirius, the state-of-the-art synchrotron light source operated by CNPEM. Using protein crystallography and X-

ray diffraction, the researchers were able to observe, on a molecular scale, how the compound binds to the parasite’s protein.

The experiments produced the first crystallographic structures of Trypanosoma cruzi KRS and allowed the identification of the protein region occupied by the molecule. The results function as a molecular map to guide the development of new compounds.

“It’s not enough to know that a molecule eliminates the parasite. When we can identify exactly which protein it targets and how this interaction occurs, we open up the possibility of designing more efficient and specific molecules for that mechanism”, explains Gustavo Mercaldi, Gustavo Mercaldi, also researcher at CNPEM, who co-coordinates the study.

The molecule studied had already been investigated in research related to malaria and cryptosporidiosis. The identification of a similar mechanism in T. cruzi allowed scientists to carry out a process known as compound repositioning.

“Repositioning may be especially relevant for neglected diseases. Instead of starting all the research from scratch, it is possible to investigate molecules that have already shown activity against other organisms and verify if the mechanisms involved can also be explored in a new disease”, explain the researchers.