Selected projects aim to repurpose existing drugs for treatment of COVID-19, find novel compounds with therapeutic potential and develop alternative diagnostic methods. The call remains open until June 22 (photo: Leo Ramos Chaves / Pesquisa FAPESP)
Published on 03/25/2021
Agência FAPESP – By April 28 FAPESP had approved 30 research grants for proposals submitted in response to the call “Fast track supplements for projects against COVID-19” issued on March 21 to expedite the funding, in the state of São Paulo, Brazil, of studies that help combat the pandemic caused by the novel coronavirus SARS-CoV-2.
A group in the University of São Paulo’s São Carlos Chemistry Institute (IQSC-USP), coordinated by Carlos Alberto Montanari, will refine and test molecules with the potential to inhibit the action of cysteine proteases, enzymes that degrade proteins and are essential to the novel coronavirus’s biological cycle. The researchers will mine a library of compounds created as part of a Thematic Project dedicated to the search for new drugs against Trypanosoma cruzi, the protozoan parasite that causes Chagas disease. Trials to evaluate the anti-viral effect of the molecules will be conducted at the university’s Biomedical Science Institute (ICB-USP). The group also plan to use machine learning tools to select candidates for testing against SARS-CoV-2 among drugs that are in the clinical trial stage.
A group coordinated by Cristiane Rodrigues Guzzo Carvalho at ICB-USP are working with Edison Durigon on the development of a rapid COVID-19 diagnostic test. The group have already cloned four fragments of the SARS-CoV-2 spike protein found to be immunogenic (capable of inducing an immune response) against serum from a human patient, and produced them on a large scale.
The viral proteins produced in the laboratory are being inoculated in rats, rabbits and goats. The group expect to have enough serum to produce the first rapid tests in under a month. The research effort also involves Shaker Chuck Farah, a professor in the University of São Paulo’s Chemistry Institute (IQ-USP).
Dario Simões Zamboni, a researcher in the University of São Paulo’s Ribeirão Preto Medical School (FMRP-USP), will study the mechanisms involved in the intense inflammatory process observed in patients with severe COVID-19. He and his group will analyze samples from patients and conduct experiments with cultured cells to find out whether the immune response to SARS-CoV-2 involves activation of a protein complex known as the inflammasome. The project will also monitor activation of the inflammasome in 60 patients admitted to Hospital das Clínicas, which is run by FMRP-USP, and treated for COVID-19 with chloroquine, either alone or in conjunction with colchicine, a drug widely used to treat diseases mediated by a specific type of inflammasome. Zamboni is also affiliated with the Center for Research on Inflammatory Diseases (CRID), a Research, Innovation and Dissemination Center (RIDC) funded by FAPESP.
Investigating the prevalence of SARS-CoV-2 in the population of blood donors attending Fundação Pró-Sangue, the blood center at the general hospital run by the University of São Paulo’s Medical School in São Paulo City (Hospital das Clínicas, FM-USP), is one of the goals of a project led by Ester Sabino at FM-USP. The group also plan to analyze blood samples from subjects who test positive for the coronavirus in order to find out if they can be used to produce hyperimmune serum (containing high amounts of antibodies against SARS-CoV-2) and to develop a test to detect such antibodies. Serological testing is considered a key source of data for epidemiological studies on the coronavirus because it helps determine the proportion of the population that is still susceptible to the disease.
Glaucius Oliva, a professor in the University of São Paulo’s São Carlos Physics Institute (IFSC-USP) and principal investigator for the RIDC Center for Innovation in Biodiversity and Drug Discovery (CIBFar), will coordinate the search for anti-virals to treat COVID-19. High-content screening will be deployed to analyze 4,000 compounds with unknown action using human cells and viral cells isolated from Brazilian patients. In addition, the researchers will analyze libraries of FDA-approved compounds, libraries established by Medicines for Malaria Ventures (MMV) and other collections created by ongoing projects in the state of São Paulo in search of new candidate drugs and opportunities to repurpose drugs approved for human use.
Drug repurposing is also the aim of a project led by Helena Nader at the Federal University of São Paulo’s Institute of Pharmacology and Molecular Biology (INFAR-UNIFESP). One of the compounds to be evaluated is heparin, an anti-coagulant also known to have anti-inflammatory and anti-viral properties. Preliminary findings suggest the SARS-CoV-2 surface protein that infects host cells binds to heparin.
Rodrigo Portes Ureshino, a researcher in the Federal University of São Paulo’s Institute of Environmental, Chemical and Pharmaceutical Sciences (ICAQF-UNIFESP), will look for compounds with estrogen-like activity and inhibitors of autophagy, the process that removes dysfunctional components of cells. This project also includes drug repurposing. At the general and teaching hospital of the University of São Paulo’s Medical School in São Paulo City (Hospital das Clínicas, FM-USP), medical doctor Heraldo Possolo de Souza will coordinate four subprojects involving patients admitted for treatment in the emergency room. The first will investigate whether inflammatory response markers measured in blood serum can predict COVID-19 patient outcomes, singly or as a group. The second will try to determine whether lung ultrasound scans are a feasible means of examining respiratory function in these patients. The third is a clinical trial of a drug used to treat other diseases and potentially useful to prevent respiratory failure in patients with COVID-19 pneumonia. The fourth will focus on statistical and stochastic models designed to enhance and orient treatment of COVID-19 patients.
José Carlos Nicolau, also a researcher at FM-USP, will coordinate efforts to develop new rapid diagnostic techniques and predict patients’ propensity to progress to severe COVID-19. The group will also investigate blood coagulation disturbances in hospitalized patients (read more at: agencia.fapesp.br/32901/).
José Luiz Proença Módena, a professor in the University of Campinas’s Biology Institute (IB-UNICAMP), will coordinate a large task force involving various units of the institution. Its goals include analyzing the circulation and genetic diversity of SARS-CoV-2 in Campinas, identifying biomarkers as aids to rapid diagnosis or prediction of fatal cases, and finding new anti-viral medications by means of drug repurposing, computational screening of novel compounds and experiments with culture cells (read more at: agencia.fapesp.br/32998).
Investigating the molecular mechanisms involved in SARS-CoV-2 infection of cultured macrophages (front-line defenders of innate immunity), lung epithelial cells (preferred targets of the virus) and cells of the central nervous system (neurons and astrocytes) in order to identify novel therapeutic targets is the aim of a project coordinated by Daniel Martins-de-Souza at IB-UNICAMP. To this end the group will analyze proteomics (the set of proteins expressed in a biological sample) and metabolomics (all metabolites in a sample), and conduct experiments in animal models.
Marcelo Mori, also a researcher at IB-UNICAMP, will investigate how aging contributes to infection by SARS-CoV-2. The research will combine analysis of patient data and pre-clinical models in search of proteins and signaling pathways that can be modulated by existing drugs to reverse the alterations induced by aging (read more at: agencia.fapesp.br/33050).
The impact of gut microbiota and its metabolites on SARS-CoV-2 infection is the focus for a project led by Marco Aurélio Ramirez Vinolo, another researcher affiliated with IB-UNICAMP. Previous studies by the group showed that microorganisms in the intestines and certain substances they secrete can afford protection against respiratory infections. The group plan to conduct experiments with mice and human cell lines infected by SARS-CoV-2.
Another study will be conducted at IB-UNICAMP, with Pedro Manoel Mendes de Moraes Vieira as principal investigator, to identify novel therapeutic targets relating to the risk factors associated with severe COVID-19 and metabolic pathways activated in the immune response to the virus.
In a neighborhood of São José do Rio Preto, a city in the northwest of the state of São Paulo, an epidemiological study of COVID-19 will be conducted with a group of volunteers who are already being followed for a Thematic Project on dengue coordinated by Maurício Lacerda Nogueira, a professor in the São José do Rio Preto Medical School (FAMERP). The participants will be observed to see if COVID-19 symptoms appear. Patients admitted to FAMERP’s hospital with suspected or confirmed COVID-19 will also be followed. Samples will be collected for analysis of pro-inflammatory cytokines, which are potential biomarkers for predicting disease severity.
Development of a simple low-cost alternative methodology for diagnosing COVID-19 is the aim of a project coordinated by Ronaldo Censi Faria at the Federal University of São Carlos’s Center for Exact Sciences and Technology (CCET-UFSCar). The platform to be built will use affordable materials and simple equipment, and will be capable of analyzing several samples concurrently.
The call will remain open until June 22, 2020, for short-term research projects as supplements to ongoing grants for Thematic Projects, Young Investigators, Research, Innovation and Dissemination Centers (RIDCs), and Engineering Research Centers (ERCs).
Projects must redirect part of their research efforts to contribute significantly to the understanding and surmounting of the risk represented by SARS-CoV-2 and/or possible ways of managing or preventing it.
FAPESP will invest up to BRL 10 million in the projects, which must last 24 months. Per project funding is capped at BRL 100,000 per year. Over and above this limit, researchers can apply for a postdoctoral scholarship, which lasts 24 months. More information can be found in Portuguese at: www.fapesp.br/14082.