Flavonoids from Pterogyne nitens Inhibit Hepatitis C Virus Entry

Autor(es):Mostrar menos -

Shimizu, Jacqueline Farinha ^{[1, 2]} ; Lima, Caroline Sprengel ^[3] ; Pereira, Carina Machado ^[1] ; Bittar, Cintia ^[1] ; Batista, Mariana Nogueira ^[1] ; Nazare, Ana Carolina ^[3] ; Polaquini, Carlos Roberto ^[3] ; Zothner, Carsten ^{[4, 5]} ; Harris, Mark ^{[4, 5]} ; Rahal, Paula ^[1] ; Regasini, Luis Octavio ^[3] ; Gomes Jardim, Ana Carolina ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ, IBILCE, Genom Study Lab, Sao Jose Do Rio Preto, SP - Brazil

^[2] Univ Fed Uberlandia, ICBIM, Inst Biomed Sci, Lab Virol, Uberlandia, MG - Brazil

^[3] Sao Paulo State Univ, IBILCE, Lab Green & Med Chem, Sao Jose Do Rio Preto, SP - Brazil

^[4] Univ Leeds, Astbury Ctr Struct Mol Biol, Leeds LS2 9JT, W Yorkshire - England

^[5] Univ Leeds, Sch Mol & Cellular Biol, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire - England

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 7, NOV 23 2017.
• Citações Web of Science: 3

Resumo

Hepatitis C virus (HCV) is one of the leading causes of liver diseases and transplantation worldwide. The current available therapy for HCV infection is based on interferon-alpha, ribavirin and the new direct-acting antivirals (DAAs), such as NS3 protease and NS5B polymerase inhibitors. However, the high costs of drug design, severe side effects and HCV resistance presented by the existing treatments demonstrate the need for developing more efficient anti-HCV agents. This study aimed to evaluate the antiviral effects of sorbifolin (1) and pedalitin (2), two flavonoids from Pterogyne nitens on the HCV replication cycle. These compounds were investigated for their anti-HCV activities using genotype 2a JFH-1 subgenomic replicons and infectious virus systems. Flavonoids 1 and 2 inhibited virus entry up to 45.0% and 78.7% respectively at non-cytotoxic concentrations. The mechanism of the flavonoid 2 block to virus entry was demonstrated to be by both the direct action on virus particles and the interference on the host cells. Alternatively, the flavonoid 1 activity was restricted to its virucidal effect. Additionally, no inhibitory effects on HCV replication and release were observed by treating cells with these flavonoids. These data are the first description of 1 and 2 possessing in vitro anti-HCV activity. (AU)

• Processo FAPESP: 12/01403-9 - Estudo do papel das proteínas do Vírus da Hepatite C no desenvolvimento de hepatocarcinoma
• Beneficiário: Cintia Bittar Oliva
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 14/22198-0 - Potencial terapêutico de fármacos flavonóidicos na infecção com o vírus da hepatite C
• Beneficiário: Paula Rahal
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/03897-1 - Atividade de toxinas de veneno de Crotalus durissus terrificus na replicação do HCV
• Beneficiário: Jacqueline Farinha Shimizu
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 14/05445-3 - Atividade anti-HCV de sorbifolina, pedalitina e seus derivados peracetilados
• Beneficiário: Caroline Sprengel Lima
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica