Natural compounds isolated from Brazilian plants are potent inhibitors of hepatitis C virus replication in vitro

Autor(es)

Jardim, A. C. G. ^{[1, 2]} ; Igloi, Z. ^{[3, 4]} ; Shimizu, J. F. ^[1] ; Santos, V. A. F. F. M. ^[5] ; Felippe, L. G. ^[5] ; Mazzeu, B. F. ^[1] ; Amako, Y. ^[6] ; Furlan, M. ^[5] ; Harris, M. ^{[3, 4]} ; Rahal, P. ^[1]

Afiliação do(s) autor(es)

^[1] UNESP Sao Paulo State Univ, Inst Biosci Language & Exact Sci IBILCE, Dept Biol, Sao Jose Do Rio Preto, SP - Brazil

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

^[3] Univ Leeds, Fac Biol Sci, Sch Mol & Cellular Biol, Leeds LS2 9JT, W Yorkshire - England

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

^[5] UNESP Sao Paulo State Univ, Inst Chem, Dept Organ Chem, Araraquara, SP - Brazil

^[6] Tokyo Metropolitan Inst Med Sci, Dept Microbiol & Cell Biol, Tokyo 113 - Japan

• Tipo de documento: Artigo Científico
• Fonte: Antiviral Research; v. 115, p. 39-47, MAR 2015.
• Citações Web of Science: 15

Resumo

Compounds extracted from plants can provide an alternative approach to new therapies. They present characteristics such as high chemical diversity, lower cost of production and milder or inexistent side effects compared with conventional treatment. The Brazilian flora represents a vast, largely untapped, resource of potential antiviral compounds. In this study, we investigate the antiviral effects of a panel of natural compounds isolated from Brazilian plants species on hepatitis C virus (HCV) genome replication. To do this we used firefly luciferase-based HCV sub-genomic replicons of genotypes 2a (JFH-1), lb and 3a and the compounds were assessed for their effects on both HCV replication and cellular toxicity. Initial screening of compounds was performed using the maximum non-toxic concentration and 4 compounds that exhibited a useful therapeutic index (favourable ratio of cytotoxicity to antiviral potency) were selected for extra analysis. The compounds APS (EC50= 2.3 mu M), a natural alkaloid isolated from Maytrenus ilicifolia, and the lignans 3{*}43 (EC50= 4.0 mu M), 3{*}20 (EC50= 8.2 mu M) and 5{*}362 (EC50= 38.9 mu M) from Peperomia blanda dramatically inhibited HCV replication as judged by reductions in luciferase activity and HCV protein expression in both the subgenomic and infectious systems. We further show that these compounds are active against a daclatasvir resistance mutant subgenomic replicon. Consistent with inhibition of genome replication, production of infectious JFH-1 virus was significantly reduced by all 4 compounds. These data are the first description of Brazilian natural compounds possessing anti-HCV activity and further analyses are being performed in order to investigate the mode of action of those compounds. (C) 2015 The Authors. Published by Elsevier B.V. (AU)

• Processo FAPESP: 11/00313-3 - Análise dos efeitos antivirais de compostos naturais brasileiros na infecção pelo Vírus da Hepatite C
• Beneficiário: Ana Carolina Gomes Jardim
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 11/11753-4 - Análise da inibição do ciclo replicativo do vírus da hepatite C por meio de compostos naturais
• Beneficiário: Paula Rahal
• Linha de fomento: Auxílio à Pesquisa - Regular