Mechanism and Molecular Interactions of Bioactive molecules with NS3 protease from Zika virus.

• Grant number: 16/12904-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): January 01, 2017
• Effective date (End): January 01, 2020
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Raghuvir Krishnaswamy Arni
• Grantee: Monika Aparecida Coronado
• 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): 18/12659-0 - Mechanisms and Molecular Interactions of Bioactive Molecules with Protein NS3 from Zika Virus - De novo drug design-, BE.EP.PD

Abstract

Since 1981, the Brazilian population has had dengue fever epidemics and all control efforts have been unsuccessful. In 2014, chikungunya fever was reported for the first time in the country. Zika virus was also reported in 2015, along with an increase of microcephaly and brain damage in newborn babies. Literature shows that Flaviviruses cause a variety of diseases, including fevers, encephalitis, and hemorrhagic fevers. NS3 is one of the Non-structural protein presents a multifunctional behaviour with an N-terminal protease domain (NS3pro) that is responsible for proteolytic processing of the viral polyprotein. Therefore, NS3 protein is the preferential choice for inhibition to stop the proteolytic processing. The multiple roles played by the NS2B-NS3 protein in the virus life cycle makes it an attractive target for antiviral drug discovery. The N-terminal region of NS3 and its cofactor NS2B constitute the protease that cleaves the viral polyprotein. No effective antiviral therapy is currently available for treatment of flavivirus infections. Development of antiviral treatment against these viruses is urgently needed. Animals venoms contain a huge variety of molecules affecting vital physiological systems, and these toxins can be a life-saving therapeutics. Since the approval of captopril - the first drug based on snake venom protein - more than 30 years ago, animals venom toxins have become a valuable natural pharmacopeia of bioactive molecules that provide lead compounds for the development of new drugs. A number of new drugs are constantly emerging from this pipeline.

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)

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, OCT 2021. (18/07572-3, 19/05614-3, 18/12659-0, 16/12904-0)

CORONADO, MONIKA APARECIDA; OLIVIER, DANILO DA SILVA; EBERLE, RAPHAEL JOSEF; DO AMARAL, MARCOS SERROU; ARNI, RAGHUVIR KRISHNASWAMY. Modeling and molecular dynamics indicate that snake venom phospholipase B-like enzymes are Ntn-hydrolases. Toxicon, v. 153, p. 106-113, OCT 2018. (16/08104-8, 16/12904-0, 15/18868-2, 09/53989-4, 15/13765-0)

EBERLE, RAPHAEL J.; CORONADO, MONIKA A.; PEINADO, RAFAELA S.; DE MORAES, FABIO R.; OLIVIER, DANILO; DREYER, THIAGO; LOPES, DEBORA DE OLIVEIRA; ROSA DA LUZ, BRENDA SILVA; AZEVEDO, VASCO; ARNI, RAGHUVIR K.. The polyanions heparin and suramin impede binding of free adenine to a DNA glycosylase from C. pseudotuberculosis. International Journal of Biological Macromolecules, v. 125, p. 459-468, MAR 15 2019. (09/53989-4, 15/18868-2, 16/08104-8, 15/13765-0, 16/12904-0)

CORONADO, MONIKA APARECIDA; EBERLE, RAPHAEL JOSEF; BLEFFERT, NICOLE; FEUERSTEIN, SOPHIE; OLIVIER, DANILO SILVA; DE MORAES, FABIO ROGERIO; WILLBOLD, DIETER; ARNI, RAGHUVIR KRISHNASWAMY. Zika virus NS2B/NS3 proteinase: A new target for an old drug - Suramin a lead compound for NS2B/NS3 proteinase inhibition. Antiviral Research, v. 160, p. 118-125, DEC 2018. (16/08104-8, 15/13765-0, 15/18868-2, 09/53989-4, 16/12904-0)

EBERLE, RAPHAEL J.; KAWAI, LIEGE A.; DE MORAES, FABIO R.; TASIC, LJUBICA; ARNI, RAGHUVIR K.; CORONADO, MONIKA A.. Biochemical and biophysical characterization of a mycoredoxin protein glutaredoxin A1 from Corynebacterium pseudotuberculosis. International Journal of Biological Macromolecules, v. 107, p. 9-pg., 2018-02-01. (09/53989-4, 15/13765-0, 16/08104-8, 15/18868-2, 16/12904-0)

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, MAR 4 2021. (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, AUG 2020. (18/07572-3, 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, v. 39, n. 18, p. 6974-6986, DEC 12 2021. (18/07572-3, 16/12904-0)

EBERLE, RAPHAEL J.; KAWAI, LIEGE A.; DE MORAES, FABIO R.; OLIVIER, DANILO; DO AMARAL, MARCOS S.; TASIC, LJUBICA; AMI, RAGHUVIR K.; CORONADO, MONIKA A.. Inhibition of thioredoxin A1 from Corynebacterium pseudotuberculosis by polyanions and flavonoids. International Journal of Biological Macromolecules, v. 117, p. 1066-1073, OCT 1 2018. (09/53989-4, 15/18868-2, 16/08104-8, 15/13765-0, 16/12904-0)

PEINADO, RAFAELA DOS S.; OLIVIER, DANILO S.; EBERLE, RAPHAEL J.; DE MORAES, FABIO R.; AMARAL, MARCOS S.; ARNI, RAGHUVIR K.; CORONADO, MONIKA A.. Binding studies of a putative C. pseudotuberculosis target protein from Vitamin B-12 Metabolism. SCIENTIFIC REPORTS, v. 9, APR 23 2019. (09/53989-4, 15/18868-2, 16/08104-8, 15/13765-0, 16/12904-0)

EBERLE, RAPHAEL J.; KAWAI, LIEGE A.; DE MORAES, FABIO R.; TASIC, LJUBICA; ARNI, RAGHUVIR K.; CORONADO, MONIKA A.. Biochemical and biophysical characterization of a mycoredoxin protein glutaredoxin A1 from Corynebacterium pseudotuberculosis. International Journal of Biological Macromolecules, v. 107, n. B, p. 1999-2007, FEB 2018. (16/08104-8, 15/13765-0, 15/18868-2, 09/53989-4, 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, MAY 2021. (16/12904-0, 19/05614-3, 18/12659-0, 18/07572-3)