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Interaction study between polyphenolic compounds and Human Respiratory Syncytial Virus M protein: search of binding sites for protein-protein oligomerization prevent.


Human Respiratory Syncytial Virus (hRSV) is the major causative agent of lower respiratory tract infections in children and immunocompromised patients. Belonging to the Pneumoviridae family, RSV is an enveloped virus with a helical nucleocapsid. Its genome consists of a negative single stranded on-segmented RNA, composed of approximately 15,200 nucleotides and 10 genes, which encode 11 proteins. One of the key factors that contribute to the success of viral replication is the M protein that acts in the stage of preparation for viral budding, coordinating the transfer of ribonucleoprotein complexes (RNPs) to lipid rafts, where the virions will be released. Therefore, M is essential for viral budding, stimulating the ideal membrane curvature for the formation of viral particles. It's known that M protein interacts with the host cell cytoskeleton to effect the conduction of the complex formed between RNP-M and with the cytoplasmic regions of the viral glycoproteins, causing maturation and elongation of the viral particles to occur near the apical region of the cell membrane. Thus, in order for the addressing and budding process to be successful, M protein must interact not only with F, G and M2-1, but also with N and P and other cellular factors. Such interaction enables oligomerization, as occurs in Paramyxovirus M proteins, giving the viral particle a typical filamentous shape when it is close to the cell membrane. Our hypothesis is that a ligand capable of interacting with the M protein may be a potential candidate to prevent the budding process of the viral particle and thus prevent the success of an ongoing infection. The objectives of this work are to investigate the interaction between protein M and the phenylpropanoids: quercetin, resveratrol and chalcones, by fluorescence spectroscopy and nuclear magnetic resonance using the saturation transfer difference (STD) technique. To achieve these goals, the M protein gene will be cloned into pD441-NHT vector, the expression will proceed in Escherichia coli and the protein will be purified by affinity and molecular exclusion chromatography. The results of the present study will allow to identify the thermodynamic parameters and the epitopes of interaction between the RSV M protein and the ligands, allowing to obtain an interaction model, as well as to propose therapeutic models. (AU)

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