دانلود رایگان مقاله فعالیت ضد ویروسی فلاونوئیدهای منتخب ضد ویروس چیکونگونیا

Abstract

This study focuses on the antiviral activity of selected flavonoids against the Chikungunya virus (CHIKV), a mosquito-transmitted virus that can cause incapacitating arthritis in infected individuals. Based on the results of screening on Vero cells, the tested compounds were evaluated further with various assays, including cytotoxicity assay, virus yield assay by quantitative reverse transcription polymerase chain reaction (qRT-PCR), virus RNA replication assay with a CHIKV replicon cell line, Western blotting, and quantitative immunofluorescence assay. Baicalein, fisetin, and quercetagetin displayed potent inhibition of CHIKV infection, with 50% inhibitory concentrations [IC50] of 1.891 mg/ml (6.997 mM), 8.444 mg/ml (29.5 mM), and 13.85 mg/ml (43.52 mM), respectively, and with minimal cytotoxicity. The time-of-addition studies and various antiviral assays demonstrated that baicalein and quercetagetin mainly inhibited CHIKV binding to the Vero cells and displayed potent activity against extracellular CHIKV particles. The qRT-PCR, immunofluorescence assay, and Western blot analyses indicated that each of these flavonoids affects CHIKV RNA production and viral protein expression. These data provide the first evidence of the intracellular anti-CHIKV activity of baicalein, fisetin, and quercetagetin.

4. Discussion

With the lack of a vaccine and antiviral treatment for CHIKV infection, various alternatives have been evaluated to increase the likelihood of finding an effective antiviral agent. In this experiment, one flavone (baicalein) and two flavonols (fisetin and quercetagetin) were selected for evaluation of their anti-CHIKV activities. During the primary antiviral screening assay, these three compounds were selected for antiviral candidates because they displayed a dose-dependent inhibition against CHIKV replication with minimal toxicity and were thus regarded as having potential for use as therapeutic agents. Based on a rapid antiviral screening test, a CHIKV replicon cell line that eliminates the viral entry and particle release steps was also used. Although the reduction of Rluc activity was not signifi- cant after treatment with either fisetin or quercetagetin compared to baicalein, it can be suggested that the observed antiviral properties from those two compounds, especially fisetin, could be a result of their effects against important cellular factors involved in CHIKV replication.