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

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)

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Scientific publications (6)
(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)
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 Zika virus in urine from randomly tested individuals in Mirassol, Brazil. INFECTION, JUL 2021. Web of Science Citations: 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. Web of Science Citations: 0.
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; BITTAR, CINTIA; NOGUEIRA, MAURICIO L.; CARNEIRO, BRUNO M.; MARIUTTI, RICARDO B.; ARNI, RAGHUVIR KRISHNASWAMY; CALMON, MARILIA FREITAS; RAHAL, PAULA. Natural Products Isolated from Oriental Medicinal Herbs Inactivate Zika Virus. Viruses-Basel, v. 11, n. 1 JAN 2019. Web of Science Citations: 4.
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; VALENCIO, CARLOS ROBERTO; NETO, PAULO SCARPELINI; CORDEIRO, JOSE ANTONIO; NOGUEIRA, MAURICIO LACERDA; RAHAL, PAULA. 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. Web of Science Citations: 1.
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; REGASINI, LUIS OCTAVIO; GOMES JARDIM, ANA CAROLINA. Flavonoids from Pterogyne nitens Inhibit Hepatitis C Virus Entry. SCIENTIFIC REPORTS, v. 7, NOV 23 2017. Web of Science Citations: 3.
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. Web of Science Citations: 50.

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