RIO DE JANEIRO, BRAZIL – Sirius, the name of the new Brazilian synchrotron light source, of the National Center for Research in Energy and Materials (CNPEM), in Campinas, São Paulo, conducted the first experiments on one of its light lines last week. The first research station to come into operation is capable of revealing details of the structure of biological molecules, such as viral proteins.
In these initial analyses, CNPEM researchers observed crystals of a protein indispensable for the life cycle of SARS-CoV-2, the novel coronavirus. The first results revealed details of this protein’s structure, crucial to understanding the virus’ biology and to support research that seeks new drugs for Covid-19, caused by the novel coronavirus.
The first research station to come into operation at Sirius is the Manacá light line, dedicated to protein crystallography. Using X-ray diffraction, this light line is able to uncover the position of each of the atoms that make up the studied protein, which helps researchers to investigate its impact on the body and its interaction with molecules that have potential for drug development.
In addition to Sirius, there are other accelerators worldwide studying the coronavirus molecules. “There are over 200 structures of pieces of the coronavirus deposited in the international database, but our [synchrotron light source], is now one of the best in terms of resolution, we are now competitive compared to other experiments. It is a race, there are many researchers around the world trying to do this, we are picking up clues, and this is being done on several accelerators. The researchers want to look at the structure and test binders that could be candidates for drugs,” said Ana Carolina Zeri, the CNPEM researcher who coordinates the first research station to begin operating.
In this first experiment in Brazil, the 3CL Protease from the SARS-CoV-2 was analyzed. “Also known as Mpro, this molecule, in a heart-shaped format, is one of the virus’ principal proteases, crucial to its life cycle. These proteases, key to viral replication, are known targets for drug development, since by inhibiting these proteins, it is possible to interfere with virus proliferation. Even the first HIV drugs were developed by targeting the virus’ proteases and the drugs with such action are present in the cocktails used for HIV until today,” explained Daniela Trivella, a CNPEM researcher with the task force against Covid-19.
The start of experiments at the Sirius facility involves a thorough testing process, in which thousands of parameters are assessed to ensure the production of accurate data. “To confirm that the research station is within the projected parameters, producing reliable results, we first solved the well-known protein structure, such as lysozyme – a molecule present in our tears and saliva. We reproduced the expected measurements for these standard samples and then, when checking the correct performance of the machine, we proceeded to collect data from real experiments with SARS-CoV-2 protein crystals,” explains Ana Carolina Zeri.
The sample analyzed in the first experiments at the Sirius was the 3CL protein of SARS-CoV-2. Produced and crystallized at CNPEM’s National Laboratory of Biocences (LNBio), 3CL is a part of the virus replication process within the body during infection.
“Initially, we reproduce the protein structure already known, to test the results produced by Manacá. By obtaining reliable and competitive data, we will enhance the molecular and structural biology studies that comprise our task force against SARS-CoV-2. We have several groups of researchers mobilized to investigate the molecular mechanisms related to the protein’s activity, to seek inhibitors to its activity, to study other viral proteins, and to produce knowledge that can support the development of drugs against the disease,” said Kleber Franchini, LNBio’s director.
The CNPEM’s next research steps are part of the MCTI Virus Network, a strategic advisory committee of the Ministry of Science, Technology and Innovation that works in the articulation of Research Units involved in the fight against coronavirus.
“In addition to our commitment to the public agenda of research with SARS-CoV-2, coordinated by the MCTI, the beginning of the Manacá operation will benefit the scientific community throughout the country. Researchers dedicated to studying the molecular details related to the disease will be able to submit research proposals to use this light line as of next week,” announced the Head of the Soft and Biological Materials Division of the National Synchrotron Light Laboratory (LNLS) at CNPEM, Mateus Cardoso.
To use the Sirius, the research proposals from the scientific community will undergo a technical evaluation by LNLS experts. “At this time, we consider that the machine is in a scientific commissioning stage (final testing stage), conducting experiments under conditions that are still imposing some limitations. However, in response to the crisis caused by Covid-19, we have decided to make this tool available earlier to researchers who are already familiar with experiments in protein crystallography, so that they can proceed with the molecular understanding of the virus,” said the Director of LNLS, Harry Westfahl Jr.
Among the 13 Sirius research stations planned for the first stage of the project, two of them have been prioritized since the start of the pandemic, as they allow studies on the virus and its interaction with human cells. In addition to Manacá, the project team is running against time to deliver the Catereté light line, focused on X-Ray Coherent Radiation techniques, where high resolution, three-dimensional cellular images can be produced.
The CNPEM and Sirius project general director, José Roque, stresses that in response to an emergency situation, the scientific community is being called upon to submit its SARS-CoV-2 research proposals. “We have begun to offer unprecedented research conditions for researchers in the country. At this time, when so much is said about the significance of science and technology in solving problems, we are before an advanced machine, designed by Brazilians and built in partnership with the domestic industry. I hope that all sectors of society will increasingly recognize the importance of science in solving our problems and our capabilities in the country,” he concludes.
Designed and built by Brazilians, funded by the Ministry of Science, Technology, and Innovation, Sirius is among the most advanced synchrotron light sources in the world. This large scientific equipment has in its core a state-of-the-art electron accelerator, which generates a type of light capable of revealing the microstructure of organic and inorganic materials.
These analyses are performed in research stations, called light lines. The Sirius project will comprise several light lines, optimized for several experiments which will work independently from each other, allowing several groups of researchers to work simultaneously in different researches in the most diverse areas, such as health, energy, new materials, environment, among others.