In vitro antiviral activity of Mizoribine against BK polyomavirus / 中华器官移植杂志

ABSTRACT

Objective:To explore the in vitro antiviral activity of Mizoribine (Miz) against BK polyomavirus (BKV) and analyze preliminarily the replication stage during inhibition.Methods:The solvent of Miz, was employed as a negative control, while Sirolimus (Sir) with in vitro anti-BKV activity was applied as a positive control. Firstly, the half maximal inhibitory concentrations (IC50) of Miz and Sir were analyzed in different cell lines. Then, prior to BKV infection, cells were treated with a gradient of drug concentrations according to the IC50 results. At different timepoints post-infection, BKV replication curves were measured by quantitative detection of its DNA in supernatant while the cells were subjected to immunofluorescence for detecting the infection rate. Finally 293FT cells treated with drugs was infected by BKV single-round pseudovirus for determining the effects of Miz on the early stage of BKV infection.Results:As compared with control group, immunofluorescence showed a lowered infection rate of BKV in a Miz dose-dependent manner, viral replication curve was significantly inhibited according to the quantitative detection of viral DNA in cell supernatant. The inhibitory effect of Sir on the level of BKV infection and replication was similar to that of Miz. However, neither Miz nor Sir exhibited a significant effect on the early stage of BKV infection.Conclusions:Miz has anti-BKV activity at cellular level and the inhibitory effect does not appear in the early stage of viral infection.