Identification of a flavonoid isolated from plum (Prunus domestica) as a potent inhibitor of Hepatitis C virus entry

Abstract Hepatitis C virus (HCV) infection is a major cause of chronic liver diseases that often requires liver transplantation. The standard therapies are limited by severe side effects, resistance development, high expense and in a substantial proportion of cases, fail to clear the infection which...

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Autores principales: Mihika Bose, Mohini Kamra, Ranajoy Mullick, Santanu Bhattacharya, Saumitra Das, Anjali A. Karande
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/6c66435b3ca844cbbc0eeecc578d30ec
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Sumario:Abstract Hepatitis C virus (HCV) infection is a major cause of chronic liver diseases that often requires liver transplantation. The standard therapies are limited by severe side effects, resistance development, high expense and in a substantial proportion of cases, fail to clear the infection which bespeak the need for development of well-tolerated antivirals. Since most of the drug development strategies target the replication stage of viral lifecycle, the identification of entry inhibitors might be crucial especially in case of liver-transplant recipients. In the present study we have evaluated fruits which are known for their hepatoprotective effects in order to screen for entry inhibitors. We report the identification of a flavonoid, rutin, isolated from Prunus domestica as a new HCV entry inhibitor. Characterization and confirmation of the chemical structure was done by LC-ESI-MS, NMR and IR spectral analyses. Rutin significantly inhibited HCV-LP binding to hepatoma cells and inhibited cell-culture derived HCV (HCVcc) entry into hepatoma cells. Importantly, rutin was found to be non-toxic to hepatoma cells. Furthermore, rutin inhibits the early entry stage of HCV lifecycle possibly by directly acting on the viral particle. In conclusion, rutin is a promising candidate for development of anti-HCV therapeutics in the management of HCV infection.