tetano
Editor, Senior Moderator
Bioorg Med Chem. 2018 Jul 27. pii: S0968-0896(18)30724-7. doi: 10.1016/j.bmc.2018.07.046. [Epub ahead of print]
[h=1]Identification of influenza PA-Nter endonuclease inhibitors using pharmacophore- and docking-based virtual screening.[/h] Ferro S[SUP]1[/SUP], Gitto R[SUP]1[/SUP], Buemi MR[SUP]1[/SUP], Karamanou S[SUP]2[/SUP], Stevaert A[SUP]2[/SUP], Naesens L[SUP]2[/SUP], De Luca L[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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 IC[SUB]50[/SUB] value of 12 μM.
[h=4]KEYWORDS:[/h] Endonuclease; Influenza virus; Molecular docking; Pharmacophore modeling; Virtual screening
PMID: 30082105 DOI: 10.1016/j.bmc.2018.07.046
[h=1]Identification of influenza PA-Nter endonuclease inhibitors using pharmacophore- and docking-based virtual screening.[/h] Ferro S[SUP]1[/SUP], Gitto R[SUP]1[/SUP], Buemi MR[SUP]1[/SUP], Karamanou S[SUP]2[/SUP], Stevaert A[SUP]2[/SUP], Naesens L[SUP]2[/SUP], De Luca L[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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 IC[SUB]50[/SUB] value of 12 μM.
[h=4]KEYWORDS:[/h] Endonuclease; Influenza virus; Molecular docking; Pharmacophore modeling; Virtual screening
PMID: 30082105 DOI: 10.1016/j.bmc.2018.07.046