Unknown

Dataset Information

0

Itraconazole inhibits enterovirus replication by targeting the oxysterol-binding protein.


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.

SUBMITTER: Strating JR 

PROVIDER: S-EPMC4383725 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications


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 replicati  ...[more]

Similar Datasets

| S-EPMC6747591 | biostudies-literature
| S-EPMC9786093 | biostudies-literature
| S-EPMC10786240 | biostudies-literature
| S-EPMC6409565 | biostudies-literature
| S-EPMC4850101 | biostudies-literature
| S-EPMC8033617 | biostudies-literature
| S-EPMC7508794 | biostudies-literature
| S-EPMC9203040 | biostudies-literature
| S-EPMC9500672 | biostudies-literature
| S-EPMC4585786 | biostudies-literature