Prof. Glaucius Oliva held a speech at Fapesp Week London on February 11 with the theme:
“Structural biology and drug discovery against Zika vírus and other arboviroses”.
“We will describe our structural biology studies of Zika virus proteins, including the crystallographic structures of NS5 RNA-dependent RNA polymerase, NS3-helicase and NS3-protease, and the ensuing efforts towards the identification on inhibitors and development of novel antiviral lead candidates. We will also report our current progresses in the structural and functional studies of other arbovirus circulating in Brazil, as yellow fever and chikungunya viruses.”
Below the FAPESP Agency article.
“Deciphering biological structures in search of medicines”
By Heitor Shimizu, de Londres | Agência FAPESP
Structural biology brings together principles of molecular biology, biochemistry and biophysics to study the molecular structure and dynamics of macromolecules, particularly proteins and nucleic acids.
The goal is to understand how these molecules acquire their structure and how changes in their structure affect their functioning. Such knowledge may be employed, for example, in obtaining compounds from natural products for use in medicaments against the most diverse types of diseases.
One of the pioneers in the field in Brazil is Glaucius Oliva, full professor at the São Carlos Institute of Physics (IFSC) at the University of São Paulo (USP). He told FAPESP Week London on 11 and 12 February in the London capital that he learned about structural biology from Sir Tom Blundell, then a professor at Birkbeck College-University of London (and currently at the University of Cambridge), during his doctorate in the English institution, completed in 1988.
“British structural biology is part of the origin of structural biology in Brazil,” Oliva told Agência FAPESP. The knowledge acquired in collaboration with British scientists allowed Oliva to organize research groups in Brazil in structural biology, developing the area in the country. “From 1995 to 2017, Brazil increased by 400% the percentage of publications in the area of structural biology in the world, being currently responsible for about 2.5% of the total produced,” Oliva said.
Thirty years after studying with Blundell – and after having chaired the National Council for Scientific and Technological Development (CNPq) from 2011 to 2015 -, Oliva is currently head of the Center for Research and Innovation in Biodiversity and Drugs (CIBFar), a of the Research, Innovation and Dissemination Centers (CEPID) of FAPESP.
CIBFar is an initiative resulting from collaborative research projects involving the Laboratory of Medicinal and Computational Chemistry and the Laboratory of Molecular Biophysics of IFSC-USP, the Bioassays, Biosynthesis and Ecophysiology Center of Natural Products of the Institute of Chemistry of the Universidade Estadual Paulista ( Unesp), the Laboratory of Organic Synthesis of the Institute of Chemistry of the University of Campinas (Unicamp), the Laboratory of Natural Products and Organic Synthesis of the Federal University of São Carlos (UFSCar) and the Laboratory of Natural Products of the School of Pharmaceutical Sciences of Ribeirão Preto of USP.
“The mission of CIBFar is to promote advances that lead to effective drug discovery through basic and applied science, using biochemical, biological and pharmacological trials, as well as advanced methods in medicinal chemistry, natural product chemistry, synthetic organic chemistry, and molecular biology and structural, “he said.
Oliva explained that the researchers of the Center use basic and applied science and develop technology to study plants, microorganisms, marine organisms, peptides and synthetic compounds in search of molecules considered of interest.
“These are molecules that could serve as targets for enzymatic, phenotypic or computational inhibition assays,” he said. The ultimate goal is to allow the development of drugs against diseases such as Chagas, malaria, leishmaniasis, Zika, cancer and others.
At a presentation at FAPESP Week at the Royal Society, the British Academy of Sciences, on 11 February, Oliva gave examples of crystalline structures of enzymes obtained from tropical parasites that were uncovered by CIBFar scientists, such as glyceraldehyde- 3-phosphate dehydrogenase, obtained from Trypanosoma cruzi, a protozoan that transmits Chagas disease, or adenine-phosphororibosyl transferase, obtained from Leishmania, a parasite that causes leishmaniasis. “More recently we have conducted structural biology studies of Zika virus proteins, including the crystallographic structures of NS5-dependent RNA polymerase (RdPd) [the enzyme found in virus that catalyzes RNA replication], NS3-helicase [ present in the zika virus, is an enzyme that promotes the opening of the RNA helix in the replication process] and NS3-protease [an enzyme synthesized by the virus to activate all vital proteins].
“Our efforts seek to identify inhibitors and develop new candidates for antivirals. In addition to the Zika virus, we have made important progress in structural and functional studies of other arboviruses circulating in Brazil, such as those that cause yellow fever and chikungunya, “Oliva said.
Full text in: http://agencia.fapesp.br/decifrar-estruturas-biologicas-em-busca-de-medicamentos/29779/