Glutathione facilitates enterovirus assembly by binding at a druggable pocket
© The Author(s) 2020..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:3 |
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| Enthalten in: |
Communications biology - 3(2020) vom: 02., Seite 9 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Duyvesteyn, Helen M E [VerfasserIn] |
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| Links: |
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| Themen: |
Antivirals |
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| Anmerkungen: |
Date Completed 14.06.2021 Date Revised 20.03.2024 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1038/s42003-019-0722-x |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM305086944 |
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| 245 | 1 | 0 | |a Glutathione facilitates enterovirus assembly by binding at a druggable pocket |
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| 500 | |a Date Revised 20.03.2024 | ||
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| 520 | |a © The Author(s) 2020. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Antivirals | |
| 650 | 4 | |a Molecular medicine | |
| 650 | 4 | |a Virus structures | |
| 650 | 4 | |a X-ray crystallography | |
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| 650 | 7 | |a VP1 protein, enterovirus B |2 NLM | |
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| 700 | 1 | |a Ren, Jingshan |e verfasserin |4 aut | |
| 700 | 1 | |a Walter, Thomas S |e verfasserin |4 aut | |
| 700 | 1 | |a Fry, Elizabeth E |e verfasserin |4 aut | |
| 700 | 1 | |a Stuart, David I |e verfasserin |4 aut | |
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