Quercetin pentaacetate inhibits in vitro human respiratory syncytial virus adhesion

Human respiratory syncytial virus (hRSV) is one of the main etiological agents of diseases of the lower respiratory tract and is often responsible for the hospitalization of children and the elderly. To date, treatments are only palliative and there is no vaccine available. Natural products show exceptional structural diversity and they have played a vital role in drug research. Several investigations focused on applied structural modification of natural products to improved metabolic stability, solubility and biological actions them. Quercetin is a flavonoid that presents several biological activities, including anti-hRSV role. Some works criticize the pharmacological use of Quercetin because it has low solubility and low specificity. In this sense, we acetylated Quercetin structure and we used in vitro and in silico assays to compare anti-hRSV function between Quercetin (QO) and its derivative molecule (Q1). Q1 shows lower cytotoxic effect than QO on HEp-2 cells. In addition, Q1 was more efficient than QO to protect HEp-2 cells infected with different multiplicity of infection (0.1-1 MOD. The virucidal effects of QO and 01 suggest interaction between these molecules and viral particle. Dynamic molecular results suggest that QO and Q1 may interact with F-protein on hRSV surface in an important region to adhesion and viral infection. Q1 interaction with F-protein showed Delta G = -14.22 kcal/mol and it was more stable than QO. Additional, MTT and plate assays confirmed that virucidal Q1 effects occurs during adhesion step of cycle hRSV replication. In conclusion, acetylation improves anti-hRSV Quercetin effects because Quercetin pentaacetate could interact with F-protein with lower binding energy and better stability to block viral adhesion. These results show alternative anti-hRSV strategy and contribute to drug discovery and development.