TORRES, Chloé; LAGADEC, Floriane; BASYUK, Eugenia; RECORDON-PINSON, Patricia; MÉTIFIOT, Mathieu

doi:10.3390/v17081138

TORRES, Chloé
Microbiologie Fondamentale et Pathogénicité [MFP]

LAGADEC, Floriane

Microbiologie Fondamentale et Pathogénicité [MFP]

BASYUK, Eugenia
Microbiologie Fondamentale et Pathogénicité [MFP]

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Article de revue

Ce document a été publié dans

Viruses. 2025-08-20, vol. 17, n° 8

Résumé en anglais

Integrase is a key protein during HIV-1 replication as it catalyzes the integration of viral DNA into the host DNA. After several decades of research, highly potent and selective active site inhibitors have emerged. The new challenge is now to develop molecules with an original mode of action, targeting integrase out of its catalytic site. During a previous study, we developed an in vitro assay to monitor the interaction between HIV-1 integrase and one of its cellular partners, GCN2. This AlphaLISA-based assay was validated as a platform for chemical modulator screening. In the present study, we used a library of natural products from the Developmental Therapeutics Program (NIH) to identify novel chemical leads. The best modulators were characterized and a structure-activity relationship study was initiated with a limited number of derivatives. We found that most inhibitors were tricylic or tetraclyclic molecules, with the most potent belonging to the anthracyclines/anthraquinones. Of note, several molecules exhibited interesting cellular activities and may be suitable for further optimization.< Réduire

Mots clés en anglais

HIV Integrase

Humans

HIV Integrase Inhibitors

HIV-1

Structure-Activity Relationship

Protein Binding

Protein Serine-Threonine Kinases

Virus Replication

URI

https://oskar-bordeaux.fr/handle/20.500.12278/207542

DOI

http://dx.doi.org/10.3390/v17081138

Unités de recherche

MFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234

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Isolation of New Chemical Modulators of the Interaction Between HIV-1 Integrase and the Cellular Restriction Factor GCN2.

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Mots clés en anglais

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