Identification of influenza PA-Nter endonuclease inhibitors using pharmacophore- and docking-based virtual screening |
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Authors: | Stefania Ferro Rosaria Gitto Maria Rosa Buemi Spyridoula Karamanou Annelies Stevaert Lieve Naesens Laura De Luca |
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Institution: | 1. Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche e Ambientali (CHIBIOFARAM), Polo Universitario SS. Annunziata, Università di Messina, Viale Annunziata, I-98168 Messina, Italy;2. Rega Institute for Medical Research, KU Leuven – University of Leuven, B-3000 Leuven, Belgium |
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Abstract: | Searching for new antiviral agents, we focused our interest on the influenza PA-Nter endonuclease. Therefore, we developed a three-dimensional pharmacophore model which contains the binding features addressed to the metal-chelating active site. The obtained hypothesis has been fruitfully employed to select three “hit compounds” through an in silico screening campaign on our in-house database of small molecules. We studied the binding poses of these hit compounds using molecular docking, and subjected them to an enzymatic assay with recombinant PA-Nter endonuclease. Compound 20 proved the most active inhibitor of the endonucleolytic cleavage reaction, with an IC50 value of 12?μM. |
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Keywords: | Influenza virus Endonuclease Pharmacophore modeling Virtual screening Molecular docking |
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