Scholarship 18/07572-3 - Bioquímica, Biologia estrutural - BV FAPESP
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Exploring the non-structural protease nsP2 from Chikungunya and Mayaro viruses: structures and inhibition.

Grant number: 18/07572-3
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Start date until: October 01, 2018
End date until: September 30, 2020
Field of knowledge:Biological Sciences - Biophysics - Molecular Biophysics
Principal Investigator:Raghuvir Krishnaswamy Arni
Grantee:Raphael Josef Eberle
Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil
Associated scholarship(s):19/05614-3 - Identification of bioactive molecules which inhibit both Chikungunya and Mayaro virus activities., BE.EP.PD

Abstract

Infection by the Chikungunya virus results in considerable social and economic trauma and requires urgent attention. The lack of efficacious treatments is compounded by potential co-infection by Chikungunya and Mayaro which exacerbates and magnifies the problem since both trigger similar reactions and analogous clinical symptoms.The cleavage of the Chikungunya and Mayaro nsP-polyproteins, by the nsP2 cysteine protease is crucial for viral replication; therefore, the identification and characterization of specific inhibitors of the nsP2 cysteine protease is potentially relevant for understanding viral replication and also to serve as a platform for the development of inhibitors that can help develop drugs. A large number of compounds will be screened for binding and inhibition and will be used for structural studies to form complexes with the Chikungunya and Mayaro nsP2 cysteine proteases. These molecules will be subsequently tested in vivo for toxicity and efficacy in collaboration with Prof. Dr. Maurício Lacerda Nogueira (Faculdade de Medicina de São José do Rio Preto (FAMERP), Departamento de Doenças Infecciosas e Parasitárias, Laboratório de Pesquisas Em Virologia).Our earlier research with Zika virus(Led by Dr. M.A. Coronado) has resulted in the expression and purification of the NS2B-NS3 protease and the identification of potent inhibitors that were subsequently characterized by biochemical and biophysical techniques in collaboration with Prof. D. Willbold (Institute of Complex Systems, Structural Biochemistry, Forschungszentrum Jülich, Germany). These results form the basis of three patent applications, which are being jointly prepared for submission.

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Scientific publications (5)
(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)
EBERLE, RAPHAEL J.; OLIVIER, DANILO S.; AMARAL, MARCOS S.; WILLBOLD, DIETER; ARNI, RAGHUVIR K.; CORONADO, MONIKA A.. Promising Natural Compounds against Flavivirus Proteases: Citrus Flavonoids Hesperetin and Hesperidin. PLANTS-BASEL, v. 10, n. 10, . (18/07572-3, 19/05614-3, 18/12659-0, 16/12904-0)
BERNARDES, JULIANA S.; EBERLE, RAPHAEL J.; VIEIRA, FABIO R. J.; CORONADO, MONIKA A.. A comparative pan-genomic analysis of 53C. pseudotuberculosisstrains based on functional domains. JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, . (18/07572-3, 16/12904-0)
EBERLE, RAPHAEL J.; OLIVIER, DANILO S.; AMARAL, MARCOS S.; GERING, IAN; WILLBOLD, DIETER; ARNI, RAGHUVIR K.; CORONADO, MONIKA A.. The Repurposed Drugs Suramin and Quinacrine Cooperatively Inhibit SARS-CoV-2 3CL(pro) In Vitro. Viruses-Basel, v. 13, n. 5, . (16/12904-0, 19/05614-3, 18/12659-0, 18/07572-3)
EBERLE, RAPHAEL J.; OLIVIER, DANILO S.; PACCA, CAROLINA C.; AVILLA, CLARITA M. S.; NOGUEIRA, MAURICIO L.; AMARAL, MARCOS S.; WILLBOLD, DIETER; ARNI, RAGHUVIR K.; CORONADO, MONIKA A.. In vitro study of Hesperetin and Hesperidin as inhibitors of zika and chikungunya virus proteases. PLoS One, v. 16, n. 3, . (16/12904-0, 19/05614-3, 18/12659-0, 18/07572-3)
BERNARDES, JULIANA S.; EBERLE, RAPHAEL J.; VIEIRA, FABIO R. J.; CORONADO, MONIKA A.. A comparative pan-genomic analysis of 53C. pseudotuberculosisstrains based on functional domains. JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, v. 39, n. 18, p. 6974-6986, . (18/07572-3, 16/12904-0)

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