Researchers at USP in São Carlos combined cutting-edge technologies and demonstrated that a molecule targeted by medications behaves differently than previously theorized.
A group of researchers from the University of São Paulo in São Carlos has just presented their findings from research indicating a new understanding of the maturation process and how inhibitors act upon the Mpro protein, an essential component in the life cycle of the Sars-CoV-2 virus and the target of various efforts to develop medications to treat Covid-19. Their results appear in an article entitled “An in-solution snapshot of SARS-COV-2 main protease maturation process and inhibition,” published in the journal Nature Communications (https://doi.org/10.1038/s41467-023-37035-5).
Mpro is an abbreviation for main protease, because of its importance to the virus. Today, two medications are available which interact with this molecule to treat covid-19. Still, some of the processes in this protein’s activity are not yet entirely understood, and this was the object of the study undertaken at Sirius.
As part of the role it plays in the life cycle of the Sars-CoV-2 virus, Mpro undergoes a series of modifications until it reaches its final form. Part of this process had already been described by the group from São Carlos, directed by Professor Glaucius Oliva.
André Godoy, who led the group, was one of the first external users of Sirius, the cutting- synchrotron light source planned and built by the Brazilian Center for Research in Energy and Materials (CNPEM), an organization overseen by the Ministry of Science, Technology and Innovation (MCTI).
In September 2020 he brought approximately 200 crystals containing proteins from the Sars-CoV-2 virus for analysis in the Manacá beamline, which was developed for experiments involving X-ray diffraction crystallography. “The Manacá beamline was the first research station to open at Sirius, as the result of a task-force effort at the CNPEM to support research exploring molecular mechanisms related to covid-19. This is one of the publications that resulted from this effort,” explains Harry Westfahl, Director of the Brazilian Synchrotron Light National Laboratory (LNLS).
Read more on the LNLS website
Image: Cryomicroscopy map of the Mpro dimer interacting with the N-terminal. Image obtained from analyses conducted at Diamond and Sirius by the USP São Carlos group