Structural characterization of Zika virus proteins and search for antiviral agents

• Grant number: 16/19712-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2016
• End date: September 30, 2020
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Glaucius Oliva
• Grantee: Andre Schutzer de Godoy
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery, AP.CEPID

Abstract

The Zika Fever, caused by the Zika Virus (ZIKV), is an emerging disease that in 2016 reached all five continents, achieving the status of a pandemic disease. It not only causes Dengue-like symptoms, the ZIKV can also affect the fetus developing during pregnancy, as well as cause neurological problems in adults, such as the Guillain-Barré Syndrome. Despite the global efforts so far, the mechanism of transmission, replication, immune evasion and also possible negative effects caused by the ZIKV are not fully understood. So far, there are no treatments or efficient ways of eradicating the virus, and prevention and control of the mosquito are the only way of fighting the ZIKV. The ZIKV is a positive chain retrovirus, where its genetic material translates a single poliprotein that is cleaved into ten different proteins. Of those, two form the viral envelope, one the capsid, and seven are involved in the virus replication. The proteins of the envelope and the NS1-ladder-domain, NS3-protease and NS5-methyltransferase have had parts of their tridimensional structures solved. Our proposal is to study the not yet solved proteins of ZIKV, by using biomolecular and X-ray crystallography techniques, aiming the structural determination of those. Once determined, the tridimensional structures will be used for the study of ligands with antiviral applicability. This project is part of the CEPID CIBFar from FAPESP, and has a secondary goal of establishing the necessary bases for the study of viruses in our lab. (AU)

Scientific publications

(12)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GODOY, ANDRE S.; LIMA, GUSTAVO M. A.; OLIVEIRA, KETLLYN I. Z.; TORRES, NAIARA U.; MALUF, FERNANDO V.; GUIDO, RAFAEL V. C.; OLIVA, GLAUCIUS. Crystal structure of Zika virus NS5 RNA-dependent RNA polymerase. NATURE COMMUNICATIONS, v. 8, MAR 27 2017. (13/07600-3, 16/17153-2, 15/16811-3, 16/19712-9)

FREIRE, MARJORIE C. L. C.; NOSKE, GABRIELA D.; BITENCOURT, NATALIA V.; SANCHES, PAULO R. S.; SANTOS-FILHO, NORIVAL A.; GAWRILJUK, VICTOR O.; DE SOUZA, EDUARDO P.; NOGUEIRA, VICTOR H. R.; DE GODOY, MARIANA O.; NAKAMURA, ALINE M.; et al. Non-Toxic Dimeric Peptides Derived from the Bothropstoxin-I Are Potent SARS-CoV-2 and Papain-like Protease Inhibitors. Molecules, v. 26, n. 16, AUG 2021. (18/17095-8, 20/04602-9, 13/07600-3, 20/05761-3, 20/12519-4, 18/25600-4, 16/19712-9, 16/13884-2, 18/13588-0)

NOSKE, G. D.; NAKAMURA, A. M.; GAWRILJUK, V. O.; FERNANDES, R. S.; LIMA, G. M. A.; ROSA, H. V. D.; PEREIRA, H. D.; ZERI, A. C. M.; NASCIMENTO, A. F. Z.; FREIRE, M. C. L. C.; et al. A Crystallographic Snapshot of SARS-CoV-2 Main Protease Maturation Process. Journal of Molecular Biology, v. 433, n. 18, SEP 3 2021. (15/16811-3, 16/19712-9, 13/07600-3)

PUHL, ANA C.; BOGART, JONATHAN W.; HABERMAN, VICTORIA A.; LARSON, JACOB E.; GODOY, ANDRE S.; NORRIS-DROUIN, JACQUELINE L.; CHOLENSKY, STEPHANIE H.; LEISNER, TINA M.; FRYE, V, STEPHEN; PARISE, V, LESLIE; et al. Discovery and Characterization of Peptide Inhibitors for Calcium and Integrin Binding Protein 1. ACS Chemical Biology, v. 15, n. 6, p. 1505-1516, JUN 19 2020. (16/19712-9)

RUIZ, URIEL ENRIQUE AQUINO; SANTOS, IGOR ANDRADE; GROSCHE, VICTORIA RIQUENA; FERNANDES, RAFAELA SACHETTO; GODOY, ANDRE SCHUTZER DE; TORRES, JHOAN DAVID AGUILLON; FREIRE, MARJORIE CAROLINE LIBERATO CAVALCANTI; MESQUITA, NATHALYA CRISTINA DE MORAES ROSO; GUEVARA-VEGA, MARCO; NICOLAU-JUNIOR, NILSON; et al. Imidazonaphthyridine effects on Chikungunya virus replication: Antiviral activity by dependent and independent of interferon type 1 pathways. VIRUS RESEARCH, v. 324, p. 14-pg., 2023-01-03. (13/07600-3, 16/19712-9, 18/05130-3)

GODOY, ANDRE SCHUTZER; NAKAMURA, ALINE MINALLI; DOUANGAMATH, ALICE; SONG, YUN; NOSKE, GABRIELA DIAS; GAWRILJUK, VICTOR OLIVEIRA; FERNANDES, RAFAELA SACHETTO; PEREIRA, HUMBERTO D. MUNIZ; OLIVEIRA, KETLLYN IRENE ZAGATO; FEARON, DAREN; et al. Allosteric regulation and crystallographic fragment screening of SARS-CoV-2 NSP15 endoribonuclease. Nucleic Acids Research, v. 51, n. 10, p. 16-pg., 2023-04-28. (13/07600-3, 15/16811-3, 16/19712-9)

NOSKE, GABRIELA DIAS; GAWRILJUK, VICTOR OLIVEIRA; FERNANDES, RAFAELA SACHETTO; FURTADO, NATHALIA DIAS; BONALDO, MYRNA CRISTINA; OLIVA, GLAUCIUS; GODOY, ANDRE SCHUTZER. Structural characterization and polymorphism analysis of the NS2B-NS3 protease from the 2017 Brazilian circulating strain of Yellow Fever virus. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, v. 1864, n. 4, APR 2020. (16/19712-9, 18/05130-3, 13/07600-3)

DE GODOY, ANDRE SCHUTZER; FERNANDES, RAFAELA SACHETTO; CAMPOS AGUIAR, ANNA CAROLINE; BUENO, RENATA VIEIRA; DE MORAES ROSO MESQUITA, NATHALYA CRISTINA; CARVALHO GUIDO, RAFAEL VICTORIO; OLIVA, GLAUCIUS. Structural and mechanistic insight from antiviral and antiparasitic enzyme drug targets for tropical infectious diseases. CURRENT OPINION IN STRUCTURAL BIOLOGY, v. 59, p. 65-72, DEC 2019. (16/19712-9, 18/05130-3, 13/07600-3, 15/18192-9)

FERNANDES, RAFAELA SACHETTO; DE GODOY, ANDRE SCHUTZER; SANTOS, IGOR ANDRADE; NOSKE, GABRIELA DIAS; DE OLIVEIRA, KETLLYN IRENE ZAGATO; GAWRILJUK, VICTOR OLIVEIRA; JARDIM, ANA CAROLINA GOMES; OLIVA, GLAUCIUS. Discovery of an imidazonaphthyridine and a riminophenazine as potent anti-Zika virus agents through a replicon-based high-throughput screening. VIRUS RESEARCH, v. 299, JUL 2 2021. (18/05130-3, 16/19712-9, 13/07600-3)

FERNANDES, RAFAELA S.; NOSKE, GABRIELA D.; GAWRILJUK, VICTOR O.; DE OLIVEIRA, KETLLYN I. Z.; GODOY, ANDRE S.; MESQUITA, NATHALYA C. M. R.; OLIVA, GLAUCIUS. High-throughput Antiviral Assays to Screen for Inhibitors of Zika Virus Replication. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, v. N/A, n. 176, p. 11-pg., 2021-10-01. (13/07600-3, 16/19712-9, 18/05130-3)

FERNANDES, RAFAELA S.; FREIRE, MARJORIE C. L. C.; BUENO, V, RENATA; GODOY, ANDRE S.; GIL, LAURA H. V. G.; OLIVA, GLAUCIUS. Reporter Replicons for Antiviral Drug Discovery against Positive Single-Stranded RNA Viruses. Viruses-Basel, v. 12, n. 6, JUN 2020. (16/19712-9, 18/05130-3, 13/07600-3, 18/17095-8)

NOSKE, GABRIELA DIAS; SONG, YUN; FERNANDES, RAFAELA SACHETTO; CHALK, ROD; ELMASSOUDI, HAITEM; KOEKEMOER, LIZBE; OWEN, C. DAVID J.; EL-BABA, TARICK V.; ROBINSON, CAROL; OLIVA, GLAUCIUS; et al. An in-solution snapshot of SARS-COV-2 main protease maturation process and inhibition. NATURE COMMUNICATIONS, v. 14, n. 1, p. 13-pg., 2023-03-20. (13/07600-3, 16/19712-9)