Publication date: May 2018
Source:International Journal of Biological Macromolecules, Volume 111
Author(s): Giovana C. Guimarães, Hemily R.M. Piva, Gabriela C. Araújo, Caroline S. Lima, Luis O. Regasini, Fernando A. de Melo, Marcelo A. Fossey, Ícaro P. Caruso, Fátima P. Souza
The human Respiratory Syncytial Virus (hRSV) is the main responsible for occurrences of respiratory diseases as pneumonia and bronchiolitis in children and elderly. M2-1 protein from hRSV is an important antitermination factor for transcription process that prevents the premature dissociation of the polymerase complex, making it a potential target for developing of inhibitors of the viral replication. The present study reports the interaction of the M2-1 tetramer with pera (Q1) and tetracetylated (Q2) quercetin derivatives, which were synthesized with the objective of generating stronger bioactive compounds against oxidation process. Fluorescence experiments showed binding constants of the M2-1/compounds complexes on order of 104M−1 with one ligand per monomeric unit, being the affinity of Q2 stronger than Q1. The thermodynamic analysis revealed values of ΔH>0 and ΔS>0, suggesting that hydrophobic interactions play a key role in the formation of the complexes. Molecular docking calculations indicated that binding sites for the compounds are in contact interfaces between globular and zinc finger domains of the monomers and that hydrogen bonds and stacking interactions are important contributions for stabilization of the complexes. Thus, the interaction of the acetylated quercetin derivatives in the RNA-binding sites of M2-1 makes these potential candidates for viral replication inhibitors.
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