Maria Cristina Nonato

Maria Cristina Nonato is a Full Professor at the School of Pharmaceutical Sciences of Ribeirão Preto-USP, President of the Research Committee at the same Institution, President of the Brazilian Crystallography Association and Co-founder and Coordinator of the Structural Biology and Screening of Bioactive Compounds division at CRAFT (Center for the Research and Advancement in Fragments and Molecular Targets). She has 25 years of experience in Structural Biology, and screening of ligands by in vitro and in silico, as prototypes for drug development for the treatment of infectious diseases.

Fragment-based drug discovery. A modern approach in early drug discovery for infectious diseases.

Fragment screening is crucial for drug discovery as it enables the identification of initial small molecule hits that can serve as building blocks for optimizing drug candidates, increasing the efficiency and success rate of the drug development process.. Fragment screening methodologies encompass techniques such as NMR spectroscopy, thermal shift assays (TSA), among others and more recenlty X-ray crystallography has also been exploit to identify and characterize potential small molecule binders for drug development. At the Center for Research and Advancement of Fragments and Molecular Targets (CRAFT), we have been exploring the application of fragment screening techniques using various methods for identifying ligands targeting diverse pharmacological targets related to infectious diseases. In particular, we will showcase our work conducted with fragment screening to identify potent inhibitors of the human dihydroorotate dehydrogenase enzyme (HsDHODH), a target for antiviral development, specifically for COVID-19. Inhibitors in the nanomolar range have been identified, and the resolved crystal structure of the HsDHODH enzyme complexed with the identified ligands has provided the structural basis justifying the observed structure-activity relationship (SAR) in biochemical and biophysical studies. These findings are being utilized for the development of new generations of compounds, and their antiviral activity against SARS-CoV-2, as measured, demonstrates the proof of concept that selective inhibition of the HsDHODH enzyme can be employed as a strategy for COVID-19 treatment.