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Article Dans Une Revue Nature Communications Année : 2023

Non-covalent inhibitors of thioredoxin glutathione reductase with schistosomicidal activity in vivo

Valentina Petukhova
  • Fonction : Auteur
Sammy Aboagye
Rachel Lullo
Margaret Byrne
  • Fonction : Auteur
Federica Gabriele
  • Fonction : Auteur
Lucy Martin
Luke Harding
Vamshikrishna Gone
Bikash Dangi
  • Fonction : Auteur
Dejan Nikolic
  • Fonction : Auteur
Grégory Effantin
Wai Li Ling
Gregory Thatcher
  • Fonction : Auteur
David Williams
Pavel Petukhov

Résumé

Abstract Only praziquantel is available for treating schistosomiasis, a disease affecting more than 200 million people. Praziquantel-resistant worms have been selected for in the lab and low cure rates from mass drug administration programs suggest that resistance is evolving in the field. Thioredoxin glutathione reductase (TGR) is essential for schistosome survival and a validated drug target. TGR inhibitors identified to date are irreversible and/or covalent inhibitors with unacceptable off-target effects. In this work, we identify noncovalent TGR inhibitors with efficacy against schistosome infections in mice, meeting the criteria for lead progression indicated by WHO. Comparisons with previous in vivo studies with praziquantel suggests that these inhibitors outperform the drug of choice for schistosomiasis against juvenile worms.

Dates et versions

hal-04384317 , version 1 (10-01-2024)

Identifiants

Citer

Valentina Petukhova, Sammy Aboagye, Matteo Ardini, Rachel Lullo, Francesca Fata, et al.. Non-covalent inhibitors of thioredoxin glutathione reductase with schistosomicidal activity in vivo. Nature Communications, 2023, 14 (1), pp.3737. ⟨10.1038/s41467-023-39444-y⟩. ⟨hal-04384317⟩
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