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Glutathione facilitates enterovirus assembly by binding at a druggable pocket.

ABSTRACT: Enteroviruses cause a range of human and animal diseases, some life-threatening, but there remain no licenced anti-enterovirus drugs. However, a benzene-sulfonamide derivative and related compounds have been shown recently to block infection of a range of enteroviruses by binding the capsid at a positively-charged surface depression conserved across many enteroviruses. It has also been established that glutathione is essential for the assembly of many enteroviruses, interacting with the capsid proteins to facilitate the formation of the pentameric assembly intermediate, although the mechanism is unknown. Here we show, by high resolution structure analyses of enterovirus F3, that reduced glutathione binds to the same interprotomer pocket as the benzene-sulfonamide derivative. Bound glutathione makes strong interactions with adjacent protomers, thereby explaining the underlying biological role of this druggable binding pocket and delineating the pharmacophore for potential antivirals.

SUBMITTER: Duyvesteyn HME

PROVIDER: S-EPMC6941975 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Glutathione facilitates enterovirus assembly by binding at a druggable pocket.

Duyvesteyn Helen M E HME Ren Jingshan J Walter Thomas S TS Fry Elizabeth E EE Stuart David I DI

Communications biology 20200103

Enteroviruses cause a range of human and animal diseases, some life-threatening, but there remain no licenced anti-enterovirus drugs. However, a benzene-sulfonamide derivative and related compounds have been shown recently to block infection of a range of enteroviruses by binding the capsid at a positively-charged surface depression conserved across many enteroviruses. It has also been established that glutathione is essential for the assembly of many enteroviruses, interacting with the capsid p ...[more]

PMID: 31909201

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Dataset Information

Glutathione facilitates enterovirus assembly by binding at a druggable pocket.

Publications

Glutathione facilitates enterovirus assembly by binding at a druggable pocket.

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