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Bioorg Med Chem. 2018 Jul 27. pii: S0968-0896(18)30724-7. doi: 10.1016/j.bmc.2018.07.046. [Epub ahead of print]
Identification of influenza PA-Nter endonuclease inhibitors using pharmacophore- and docking-based virtual screening.
Ferro S1, Gitto R1, Buemi MR1, Karamanou S2, Stevaert A2, Naesens L2, De Luca L3.
Author information
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.
KEYWORDS:
Endonuclease; Influenza virus; Molecular docking; Pharmacophore modeling; Virtual screening
PMID: 30082105 DOI: 10.1016/j.bmc.2018.07.046
Identification of influenza PA-Nter endonuclease inhibitors using pharmacophore- and docking-based virtual screening.
Ferro S1, Gitto R1, Buemi MR1, Karamanou S2, Stevaert A2, Naesens L2, De Luca L3.
Author information
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.
KEYWORDS:
Endonuclease; Influenza virus; Molecular docking; Pharmacophore modeling; Virtual screening
PMID: 30082105 DOI: 10.1016/j.bmc.2018.07.046