Design, synthesis, biophysical and biological evaluation of original condensed pyrrolopyrimidine and pyrrolopyridine ligands as anti-SARS-CoV-2 agents targeting G4
The design and synthesis of novel bis[(substituted-aminomethyl)phenyl]phenyl pyrrolopyrimidines, pyrrolopyridines, pyrazolopyrimidines, imidazopyrimidines, and tris[(substituted-aminomethyl)phenyl]phenyl pyrrolopyrimidines are reported here. These original G-quadruplex (G4) ligands have been then subjected to a screening on SARS-CoV-2 using a competition HTRF assay by targeting the SUD-NM/TRF2 RNA G4 interaction. The more promising derivatives have been evaluated in vitro to determine their potential antiviral effect on two different cell lines infected by two SARS-CoV-2 strains. This study revealed a clear correlation between their antiviral property and their efficacy to prevent the SUD/G4 interaction. This correlation supports the choice of SUD/RNA G4 complexes formed during SARS-CoV-2 infection as new antiviral targets.
Authors
- Leonardo Lari (ORCID: https://orcid.org/0000-0002-1446-2877)
- Luisa Ronga (ORCID: https://orcid.org/0000-0002-8485-6492)
- Solène Savrimoutou
- Olivier Helynck
- Sandra Albenque-Rubio
- Jean Guillon
- Nicolas Da Rocha
- Jean‐Louis Mergny (ORCID: https://orcid.org/0000-0003-3043-8401)
- Mohamed G. Arab (ORCID: https://orcid.org/0000-0002-2744-5814)
- Hélène Munier‐Lehmann (ORCID: https://orcid.org/0000-0001-7579-8561)
- Stéphane Moreau (ORCID: https://orcid.org/0000-0002-9306-8375)
- Noël Pinaud (ORCID: https://orcid.org/0000-0001-7646-5312)
- Jeanne Chiaravalli (ORCID: https://orcid.org/0000-0001-9135-4565)
- Cyrielle Durand (ORCID: https://orcid.org/0000-0002-1169-041X)
- Marc Lavigne (ORCID: https://orcid.org/0000-0002-3131-2539)
- Tshering Zangmo
- Simon Chirold
Institutions
- Centre National de la Recherche Scientifique (FR)
- École Polytechnique (FR)
- Université de Pau et des Pays de l'Adour (FR)
- Université de Bordeaux (FR)
- Inserm (FR)
- Institut Pasteur (FR)
- Université Paris Cité (FR)
- Institut des Sciences Moléculaires (FR)
- Bordeaux Population Health (FR)
- Institut Polytechnique de Bordeaux (FR)
Publication Details
- Journal
- European Journal of Medicinal Chemistry
- Published
- 2025-04-23
- DOI
- https://doi.org/10.1016/j.ejmech.2025.117655
- Citations
- 2
- Primary Topic
- Cancer therapeutics and mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Agence Nationale de Recherches sur le Sida et les Hépatites Virales
- Institut Pasteur
- Centre National de la Recherche Scientifique
- Université de Bordeaux
- École Polytechnique, Université Paris-Saclay
- Agence de l'innovation de Défense