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Toward the Target: Tilorone, Quinacrine, and Pyronaridine Bind to Ebola Virus Glycoprotein.

ABSTRACT: Pyronaridine, tilorone, and quinacrine were recently identified by a machine learning model and demonstrated in vitro and in vivo activity against Ebola virus (EBOV) and represent viable candidates for drug repurposing. The target for these molecules was previously unknown. These drugs have now been docked into the crystal structure of the ebola glycoprotein and then experimentally validated in vitro using microscale thermophoresis to generate K _d values for tilorone (0.73 μM), pyronaridine (7.34 μM), and quinacrine (7.55 μM). These molecules were shown to bind with a higher affinity than the previously reported toremifene (16 μM). These three structures provide more insight into the structural diversity of ebola glycoprotein inhibitors which can be utilized in the discovery and design of additional inhibitors.

SUBMITTER: Lane TR

PROVIDER: S-EPMC7430956 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Toward the Target: Tilorone, Quinacrine, and Pyronaridine Bind to Ebola Virus Glycoprotein.

Lane Thomas R TR Ekins Sean S

ACS medicinal chemistry letters 20200723 8

Pyronaridine, tilorone, and quinacrine were recently identified by a machine learning model and demonstrated in vitro and in vivo activity against Ebola virus (EBOV) and represent viable candidates for drug repurposing. The target for these molecules was previously unknown. These drugs have now been docked into the crystal structure of the ebola glycoprotein and then experimentally validated in vitro using microscale thermophoresis to generate K d values fo ...[more]

PMID: 32832035

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