Itraconazole inhibits enterovirus replication by targeting the oxysterol-binding protein.
Cell Rep
; 10(4): 600-15, 2015 Feb 03.
Article
en En
| MEDLINE
| ID: mdl-25640182
ABSTRACT
Itraconazole (ITZ) is a well-known antifungal agent that also has anticancer activity. In this study, we identify ITZ as a broad-spectrum inhibitor of enteroviruses (e.g., poliovirus, coxsackievirus, enterovirus-71, rhinovirus). We demonstrate that ITZ inhibits viral RNA replication by targeting oxysterol-binding protein (OSBP) and OSBP-related protein 4 (ORP4). Consistently, OSW-1, a specific OSBP/ORP4 antagonist, also inhibits enterovirus replication. Knockdown of OSBP inhibits virus replication, whereas overexpression of OSBP or ORP4 counteracts the antiviral effects of ITZ and OSW-1. ITZ binds OSBP and inhibits its function, i.e., shuttling of cholesterol and phosphatidylinositol-4-phosphate between membranes, thereby likely perturbing the virus-induced membrane alterations essential for viral replication organelle formation. ITZ also inhibits hepatitis C virus replication, which also relies on OSBP. Together, these data implicate OSBP/ORP4 as molecular targets of ITZ and point to an essential role of OSBP/ORP4-mediated lipid exchange in virus replication that can be targeted by antiviral drugs.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Replicación Viral
/
Receptores de Esteroides
/
Itraconazol
/
Enterovirus
Límite:
Humans
Idioma:
En
Año:
2015
Tipo del documento:
Article