Mechanisms and Molecular Interactions of Bioactive Molecules with Protein NS3 from Zika Virus - De novo drug design-

• Grant number: 18/12659-0
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: August 30, 2018
• End date: August 26, 2019
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Raghuvir Krishnaswamy Arni
• Grantee: Monika Aparecida Coronado
• Supervisor: Dieter Willbold
• 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
• Institution abroad: Forschungszentrum Jülich, Germany
• Associated to the scholarship: 16/12904-0 - Mechanism and Molecular Interactions of Bioactive molecules with NS3 protease from Zika virus., BP.PD

Abstract

Infection by flaviviruses cause a variety of diseases, including fevers, encephalitis, and hemorrhagic fevers. NS3 is a multifunctional non-structural protein containing an N-terminal protease domain (NS3pro) that is responsible for the proteolytic processing of the viral polyprotein. NS3 protein is the preferential target for inhibition of replication by avoiding proteolytic processing and the multiple roles played by the NS2B-NS3 protein in the virus life cycle makes it an attractive target for antiviral drug development since no effective antiviral therapy is currently available. Four promising inhibitors with very low IC50 values have been selected and will be developed iteratively and optimized based on in silico and in vitro studies.

Scientific publications

(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.; 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)

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)

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)