Flavonoids from Pterogyne nitens Inhibit Hepatitis C Virus Entry

Made available in DSpace on 2018-11-29T03:50:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-11-23 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) Royal Society-Newton Advanced Fellowship Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Wellcome Trust Investigator Award 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. Sao Paulo State Univ, IBILCE, Genom Study Lab, Sao Jose Do Rio Preto, SP, Brazil Univ Fed Uberlandia, ICBIM, Inst Biomed Sci, Lab Virol, Uberlandia, MG, Brazil Sao Paulo State Univ, IBILCE, Lab Green & Med Chem, Sao Jose Do Rio Preto, SP, Brazil Univ Leeds, Sch Mol & Cellular Biol, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire, England Univ Leeds, Astbury Ctr Struct Mol Biol, Leeds LS2 9JT, W Yorkshire, England Sao Paulo State Univ, IBILCE, Genom Study Lab, Sao Jose Do Rio Preto, SP, Brazil Sao Paulo State Univ, IBILCE, Lab Green & Med Chem, Sao Jose Do Rio Preto, SP, Brazil CNPq: 445021/2014-4 FAPEMIG: APQ-00587-14 FAPEMIG: SICONV 793988/2013 Royal Society-Newton Advanced Fellowship: NA 150195 FAPESP: 2012/01403-9 FAPESP: 2013/00313-3 FAPESP: 2013/03897-1 FAPESP: 2014/05445-3 FAPESP: 2014/22198-0 Wellcome Trust Investigator Award: 096670