Identification of influenza PA-Nter endonuclease inhibitors using pharmacophore- and docking-based virtual screening.

Basic Information

ID: ALA4229507

Journal: Bioorg Med Chem

Title: Identification of influenza PA-Nter endonuclease inhibitors using pharmacophore- and docking-based virtual screening.

Authors: Ferro S, Gitto R, Buemi MR, Karamanou S, Stevaert A, Naesens L, De Luca L.

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.

CiteXplore: 30082105

DOI: 10.1016/j.bmc.2018.07.046

Patent ID: