Chalcone-derived molecules block the progress of hRSV infection

Introduction: Human Respiratory Syncytial Virus (hRSV) is the most common pathogen responsible for lower respiratory diseases in children, causing bronchiolitis and pneumonia, and associated with significant morbidity and mortality. Nearly all children by two years of age have been infected with hRSV, with ~2% requiring hospitalization. There is currently no approved vaccine for this age group and no approved antiviral drugs. Safe therapies are needed. Natural compounds, such as chalcone, have shown potential benefits against other viruses, inhibiting the viral cycle by several pathways. Objectives: The objective of this work was to investigate the effect of chalcone and its derivatives on RSV infection of cultured cells. Methodology: The most promising molecules were pre-selected by MTT assay, inoculating HEp-2 cells with an MOI of 0.2 for 1 hour and post-treating with fresh culture medium containing non-cytotoxic concentrations of the 31 tested molecules. After pre-selection, the promising molecules were tested again by plaque formation assay. Results: The MTT assay results showed that of the molecules, eight were effective post inoculation, inhibiting the progress of the infection between from 44% to 76%. Among the eight compounds effective in the MTT assay, five showed efficiencies above 50% in the plaque formation assay, ranging from 50.3% to 81.1% of cell protection. Conclusions: These results suggest that the molecules might interact with the M, M2-1/2, P, N or L proteins involved in viral replication and assembly, delaying the infection process and the formation of new infectious virus particles. These compounds warrant further analysis for prophylaxis and therapy against RSV infection.