Size and Flexibility Define the Inhibition of the H3N2 Influenza Endonuclease Enzyme by Calix[n]arenes
Yannick Tauran,
José Pedro Cerón-Carrasco,
Moez Rhimi,
Florent Perret,
Beomjoon Kim,
Dominique Collard,
Anthony W. Coleman,
Horacio Pérez-Sánchez
Affiliations
Yannick Tauran
Laboratoire Multimatériaux et Interfaces CNRS UMR 5615, Université Lyon 1, 69622 Villeurbanne, France
José Pedro Cerón-Carrasco
Bioinformatics and High Performance Computing (BIO-HPC) Research Group, Universidad Católica de Murcia (UCAM), 30107 Murcia, Spain
Moez Rhimi
Institut National de la Recherche Agronomique (INRA), UMR 1319 Micalis, F-78350 Jouy-en-Josas, France
Florent Perret
Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, CNRS UMR 5246, Université Lyon 1, 69622 Villeurbanne, France
Beomjoon Kim
Laboratory for Integrated Micro-Mechatronic Systems (LIMMS)/CNRS-IIS UMI 2820, Institute of Industrial Science, The University of Tokyo, Tokyo 153-8505, Japan
Dominique Collard
Université Lille, CNRS, Centrale Lille, Institut Supérieur de l’Electronique et du Numérique (ISEN), University Valenciennes, UMR 8520-IEMN, F59000 Lille, France
Anthony W. Coleman
Laboratoire Multimatériaux et Interfaces CNRS UMR 5615, Université Lyon 1, 69622 Villeurbanne, France
Horacio Pérez-Sánchez
Bioinformatics and High Performance Computing (BIO-HPC) Research Group, Universidad Católica de Murcia (UCAM), 30107 Murcia, Spain
Inhibition of H3N2 influenza PA endonuclease activity by a panel of anionic calix[n]arenes and β-cyclodextrin sulfate has been studied. The joint experimental and theoretical results reveal that the larger, more flexible and highly water-soluble sulfonato-calix[n]arenes have high inhibitory activity, with para-sulfonato-calix[8]arene, SC8, having an IC50 value of 6.4 μM. Molecular docking calculations show the SC8 can interact at both the polyanion binding site and also the catalytic site of H3N2 influenza PA endonuclease.
