Evaluation of the potential effects of Kaempferol and chalcones derivatives over the RSV replication cycle in cell culture: investigating proteic mediators and metabolites in the viral cycle

Abstract

HRSV is the major causes of severe Acute Respiratory Infections (ARIs) in humans, being the agent that most leads to hospitalizations worldwide after bacterial pneumonia. It is estimated that almost all children up to two years of age have become infected with hRSV, including about 2% of this requiring hospitalization. In the absence of fully formulated vaccines or antiviral compounds effective in hRSV combating, the search for molecules that perform this function is of concern and necessary. Currently, treatment of hRSV involves prophylactic measures by administration of antibodies such as Palivizumab or derivatives and the use of antivirals like Ribavirin, both of which are prescribed only to infected risk groups, since such medications are restricted because of the high cost and the possibility of cause serious side effects. Several compounds and therapies have been clinically tested and new preventive immunization strategies developed, such as maternal and pediatric vaccination. Another source of increasing research is related to plant products, since many of these compounds have shown antiviral potential, among which are derivatives of kaempferol and chalcones, which have demonstrated an effective role in combating infections caused by SARS-COV, Influenza virus and Zika virus. In this sense, the objective of this project will be to investigate the effect of derivatives of kaempferol and chalcones on the phases of the replicative cycle of hRSV. Hep-2 cells will be incubated in different concentrations of derivatives of kaempferol and chalcones in virucidal action evaluation protocols, in which the phases of the viral infection cycle (adhesion, internalization, replication and budding) will be verified at the pre and posttreatment level. The conditions that present an inhibitory effect will be used in the search for protein pathways altered by derivatives of kaempferol and chalcones by Mass Spectrometry (MS) and the metabolites generated by Nuclear Magnetic Resonance (NMR) will be evaluated. The development of this project could (AU)