Therapeutic potential of Flavonoid-like drugs on Hepatitis C virus infection

• Grant number: 14/22198-0
• Support Opportunities: Regular Research Grants
• Duration: March 01, 2015 - August 31, 2017
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Paula Rahal
• Grantee: Paula Rahal
• 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

Abstract

Hepatitis C virus (HCV) is a worldwide problem of public health and it is estimated that around 2% of world population is infected with this virus. Chronic infection can progress to hepatic cirrhosis and hepatocelular carcinoma and it is currently the major cause of liver transplantation in the occident. Current therapy based on pegylated interferon and ribavirin presents low sustained virological response, is expensive treatment and cause severe side effects. These data demonstrate the necessity of developing innovative antiviral or combination of therapies for HCV treatment. Natural flavonoids, such as epigallocatechin-3-gallate, naringenin, and quercetin can provide an alternative approach to novel antiviral therapies. They interfere with multiple HCV lifecycle steps, ranging from entry, replication and assembly to release. Therefore, this project proposes to investigate the effects of synthetic flavonoid-like compounds, including chalcones, flavanones, flavones and flavonols on HCV lifecycle, and identify the mode of action of these natural product-based compounds as antiviral agents. We will screen these compounds using both subgenomic HCV replicons and the recently developed infectious cell culture JFH-1 system. This system has provided understanding of biological aspects of HCV and offers great promise for the development of future antiviral therapies. Luciferase, western-blotting, immunofluorescence and quantification of viral load by real time PCR assays will provide results that will support the relevance of these methods for intervention with HCV infection. Finally, the design of novel drugs based on natural product scaffolds associated to new chemical entities can result in patentable compounds, which are very attractive to research, development and innovation approaches. (AU)

Scientific publications

(9)

(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)

SCARIN PROVAZZI, PAOLA JOCELAN; GONCALVES ROSSI, LIVIA MARIA; CARNEIRO, BRUNO MOREIRA; MIURA, VALERIA CHAMAS; RODRIGUES ROSA, PLINIO CESAR; DE CARVALHO, LUCAS RODRIGUES; QUEIROZ DE ANDRADE, STEPHANE TEREZA; FACHINI, ROBERTA MARIA; TOMMASINI GROTTO, REJANE MARIA; SILVA, GIOVANNI FARIA; et al. Hierarchical assessment of host factors influencing the spontaneous resolution of hepatitis C infection. Brazilian Journal of Microbiology, v. 50, n. 1, p. 147-155, JAN 2019. (14/22198-0)

SHIMIZU, JACQUELINE FARINHA; LIMA, CAROLINE SPRENGEL; PEREIRA, CARINA MACHADO; BITTAR, CINTIA; BATISTA, MARIANA NOGUEIRA; NAZARE, ANA CAROLINA; POLAQUINI, CARLOS ROBERTO; ZOTHNER, CARSTEN; HARRIS, MARK; RAHAL, PAULA; et al. Flavonoids from Pterogyne nitens Inhibit Hepatitis C Virus Entry. SCIENTIFIC REPORTS, v. 7, NOV 23 2017. (12/01403-9, 14/22198-0, 13/03897-1, 14/05445-3)

BATISTA, MARIANA N.; BRAGA, ANA CLAUDIA S.; FERNANDES CAMPOS, GUILHERME RODRIGUES; SOUZA, MARCOS MICHEL; ADUM DE MATOS, RENATA PRANDINI; LOPES, TAIRINE ZARA; CANDIDO, NATALIA MARIA; DUARTE LIMA, MARIA LETICIA; MACHADO, FRANCIELLY CRISTINA; QUEIROZ DE ANDRADE, STEPHANE TEREZA; et al. Natural Products Isolated from Oriental Medicinal Herbs Inactivate Zika Virus. Viruses-Basel, v. 11, n. 1, JAN 2019. (14/22198-0)

DA CONCEICAO, PAMELA JOYCE PREVIDELLI; DE CARVALHO, LUCAS RODRIGUES; DE GODOY, BIANCA LARA VENANCIO; NOGUEIRA, MAURICIO LACERDA; TERZIAN, ANA CAROLINA BERNARDES; DE GODOY, MOACIR FERNANDES; CALMON, MARILIA FREITAS; BITTAR, CINTIA; RAHAL, PAULA. Detection of DENV-2 and ZIKV coinfection in southeastern Brazil by serum and urine testing. MEDICAL MICROBIOLOGY AND IMMUNOLOGY, v. 212, n. 3, p. 9-pg., 2023-04-07. (14/22198-0)

DA CONCEICAO, PAMELA JOYCE PREVIDELLI; DE CARVALHO, LUCAS RODRIGUES; DE GODOY, BIANCA LARA VENANCIO; NOGUEIRA, MAURICIO LACERDA; TERZIAN, ANA CAROLINA BERNARDES; DE GODOY, MOACIR FERNANDES; CALMON, MARILIA FREITAS; BITTAR, CINTIA; RAHAL, PAULA. etection of Zika virus in urine from randomly tested individuals in Mirassol, Brazi. INFECTION, v. 50, n. 1, JUL 2021. (14/22198-0)

CARNEIRO, BRUNO M.; BATISTA, MARIANA N.; BRAGA, ANA CLAUDIA S.; NOGUEIRA, MAURICIO L.; RAHAL, PAULA. The green tea molecule EGCG inhibits Zika virus entry. VIROLOGY, v. 496, p. 215-218, SEP 2016. (14/22199-6, 14/22198-0, 13/21719-3)

LOPES, TAIRINE ZARA; DE MORAES, FABIO ROGERIO; TEDESCO, ANTONIO CLAUDIO; ARNI, RAGHUVIR KRISHNASWAMY; RAHAL, PAULA; CALMON, MARILIA FREITAS. Berberine associated photodynamic therapy promotes autophagy and apoptosis via ROS generation in renal carcinoma cells (vol 123, 109794, 2020). BIOMEDICINE & PHARMACOTHERAPY, v. 125, p. 1-pg., 2020-05-01. (14/22198-0, 15/13765-0, 15/16660-5)

DUARTE LIMA, MARIA LETICIA; CABRAL, AGATA SILVA; BITTAR, CINTIA; FALLEIROS JUNIOR, LUIZ ROBERTO; ALVES GUERRA, LUIZ HENRIQUE; CARNEIRO, BRUNO MOREIRA; DE SOUZA FERREIRA, LUIS CARLOS; NOGUEIRA, MAURICIO LACERDA; TABOGA, SEBASTIAO ROBERTO; CALMON, MARILIA FREITAS; et al. Early infection of Zika virus in the male reproductive system of AG129 mice: molecular and immunohistochemical evaluation. Brazilian Journal of Microbiology, v. N/A, p. 9-pg., 2022-04-23. (14/22198-0)

MACHADO, FRANCIELLY CRISTINA; BITTAR, CINTIA; RAHAL, PAULA; CALMON, MARILIA FREITAS. Identification of differentially expressed miRNAs in human cells infected with different Zika virus strains. ARCHIVES OF VIROLOGY, v. 166, n. 6, APR 2021. (17/09197-2, 14/22198-0, 15/16660-5)