| Congresso Brasileiro de Microbiologia 2023 | Resumo: 1126-1 | ||||
Resumo: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. The objective of this work was to investigate the virucidal effect of chalcone and its derivatives on RSV infection of cultured cells, by MTT and plate formatting assay. The 30 chalcone derivatives were separated into five groups (groups C, S, L, V, and G) according to their derivation. HEp-2 cells were adhered in 96-wells to form the monolayer. After 24 hours, direct virucidal activity was tested, adding five non-cytotoxic concentrations to a viral solution and incubating for 1 hour at 37 °C before inoculating the cells (MOI of 0.2, for 1 hour) then replacing the inoculum with fresh medium. After 48 hours of infection, cell viability was measured by MTT assay. Derivatives that showed high and average viral inhibition against viral infection were tested in plaque formatting assay. The MTT assay showed six derivatives with high virucidal potential, four of them being from the S group and two others from the V and G groups. The average effects compounds were three, one from each group with high-effect viral inhibition. The S1216 and G1544 were the derivatives with the greatest inhibition, with 63% and 44%, respectively. The results of the plate formatting assay reveal that group G, with the high and average results (G1544 and G1543) in MTT, reduced 46% and 43% the plate formatting of hRSV, as well as the derivative of group V (V1438), reducing 42%, while the others showed minimal effect or no effect. These results suggest that the molecules might block the interaction site on a cell receptor for the F or G proteins of RSV, preventing the virus from fusing with the host cell membrane, and delaying the infection process. These compounds warrant further analysis for prophylaxis and therapy against RSV infection.
Finantial support: FAPESP, CNPq, FINEP. Palavras-chave: cell virus interaction, chalcone, inhibitors, natural compounds, RSV Agência de fomento:FAPESP, CNPq, FINEP. | |||||