Binding investigation between M2-1protein from hRSV and acetylated quercetin derivatives: H-1 NMR, fluorescence spectroscopy, and molecular docking

Author(s)

Guimaraes, Giovana C. ^{[1, 2]} ; Piva, Hemily R. M. ^{[1, 2]} ; Araujo, Gabriela C. ^{[2, 3]} ; Lima, Caroline S. ^[4] ; Regasini, Luis O. ^[4] ; de Melo, Fernando A. ^{[2, 3]} ; Fossey, Marcelo A. ^{[2, 3]} ; Caruso, Icaro P. ^{[2, 3]} ; Souza, Fatima P. ^{[2, 3]}

Affiliation

^[1] UNESP, Inst Biociencias Letras & Ciencias Exatas, Dept Biol, Sao Jose Do Rio Preto, SP - Brazil

^[2] UNESP, Multiuser Ctr Biomol Innovat, Inst Biociencias Letras & Ciencias Exatas, Lab Mol Biol, Sao Jose Do Rio Preto, SP - Brazil

^[3] UNESP, Inst Biociendas Letras & Ciencias Exatas, Dept Phys, Sao Jose Do Rio Preto, SP - Brazil

^[4] UNESP, Inst Biociencias Letras & Ciencias Exatas, Dept Chem & Environm Sci, Sao Jose Do Rio Preto, SP - Brazil

• Document type: Journal article
• Source: International Journal of Biological Macromolecules; v. 111, p. 33-38, MAY 2018.
• Web of Science Citations: 0

Abstract

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 10(4) M-1 with one ligand per monomeric unit, being the affinity of Q2 stronger than Q1. The thermodynamic analysis revealed values of Delta H > 0 and Delta S > 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. (C) 2017 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 13/24355-2 - Cloning, expression and analysis of the interaction of the M2-1 protein of HRSV with Flavonides: investigation for targets in blocking viral replication
• Grantee: Fátima Pereira de Souza
• Support type: Regular Research Grants
• FAPESP's process: 09/53989-4 - Acquisition of a nuclear magnetic resonance spectrometer for studies of biomolecules
• Grantee: Raghuvir Krishnaswamy Arni
• Support type: Multi-user Equipment Program