Fluoxetine targets an allosteric site in the enterovirus 2C AAA+ ATPase and stabilizes a ring-shaped hexameric complex.


Journal

Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440

Informations de publication

Date de publication:
07 Jan 2022
Historique:
entrez: 5 1 2022
pubmed: 6 1 2022
medline: 6 1 2022
Statut: ppublish

Résumé

Enteroviruses are globally prevalent human pathogens responsible for many diseases. The nonstructural protein 2C is a AAA+ helicase and plays a key role in enterovirus replication. Drug repurposing screens identified 2C-targeting compounds such as fluoxetine and dibucaine, but how they inhibit 2C is unknown. Here, we present a crystal structure of the soluble and monomeric fragment of coxsackievirus B3 2C protein in complex with (

Identifiants

pubmed: 34985963
doi: 10.1126/sciadv.abj7615
pmc: PMC8730599
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

eabj7615

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Auteurs

Daniel L Hurdiss (DL)

Virology Section, Infectious Diseases and Immunology Division, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584CL Utrecht, Netherlands.
Cryo-Electron Microscopy, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, Netherlands.

Priscila El Kazzi (P)

Aix Marseille Université, CNRS, AFMB UMR 7257, Marseille, France.

Lisa Bauer (L)

Virology Section, Infectious Diseases and Immunology Division, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584CL Utrecht, Netherlands.

Nicolas Papageorgiou (N)

Aix Marseille Université, CNRS, AFMB UMR 7257, Marseille, France.

François P Ferron (FP)

Aix Marseille Université, CNRS, AFMB UMR 7257, Marseille, France.

Tim Donselaar (T)

Virology Section, Infectious Diseases and Immunology Division, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584CL Utrecht, Netherlands.

Arno L W van Vliet (ALW)

Virology Section, Infectious Diseases and Immunology Division, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584CL Utrecht, Netherlands.

Tatiana M Shamorkina (TM)

Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH, Utrecht, Netherlands.

Joost Snijder (J)

Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH, Utrecht, Netherlands.

Bruno Canard (B)

Aix Marseille Université, CNRS, AFMB UMR 7257, Marseille, France.

Etienne Decroly (E)

Aix Marseille Université, CNRS, AFMB UMR 7257, Marseille, France.

Andrea Brancale (A)

School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK.

Tzviya Zeev-Ben-Mordehai (T)

Cryo-Electron Microscopy, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, Netherlands.

Friedrich Förster (F)

Cryo-Electron Microscopy, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, Netherlands.

Frank J M van Kuppeveld (FJM)

Virology Section, Infectious Diseases and Immunology Division, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584CL Utrecht, Netherlands.

Bruno Coutard (B)

Unité des Virus Émergents (UVE: Aix-Marseille Univ-IRD 190-Inserm 1207), Marseille, France.

Classifications MeSH