Identification of influenza PA-Nter endonuclease inhibitors using pharmacophore- and docking-based virtual screening. Issue 15 (15th August 2018)

• Record Type: Journal Article
• Authors: Ferro, Stefania; Gitto, Rosaria; Buemi, Maria Rosa; Karamanou, Spyridoula; Stevaert, Annelies; Naesens, Lieve; De Luca, Laura
• Is Part Of: Bioorganic & medicinal chemistry. Volume 26:Issue 15(2018)
• Page Start: 4544
• Page End: 4550
• Publication Date: 2018-08-15
• Subjects: Influenza virus -- Endonuclease -- Pharmacophore modeling -- Virtual screening -- Molecular docking; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2018.07.046
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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. Compound20 proved the most active inhibitor of the endonucleolytic cleavage reaction, with an IC50 value of 12 μM.