瑞德西韦对狂犬病病毒的体外抑制作用研究

Activity of remdesivir against rabies virus in vitro

目的研究瑞德西韦对不同狂犬病病毒的体外抑制作用。方法根据药物、病毒及细胞的不同作用方式,以法匹拉韦(T705)作为阳性对照药物,使用组织培养半数感染量(TCID_(50))、直接免疫荧光法及实时荧光定量PCR等方法,分析瑞德西韦对不同狂犬病病毒的阻断吸附、抑制复制和直接杀伤作用。结果在阻断吸附和抑制复制的实验中,与相应浓度的T705阳性对照组相比,500μmol/L瑞德西韦处理BHK-21及N2a细胞后,CVS-11病毒滴度均降低(P<0.01)。分别与CVS-11及SC16街毒株感染组相比,500μmol/L瑞德西韦处理N2a细胞后病毒的滴度及mRNA拷贝数均降低(P<0.01)。在直接杀伤实验中,瑞德西韦无抑制病毒作用。结论瑞德西韦能够显著阻断狂犬病病毒的吸附并能够抑制其体外复制,但无直接杀伤狂犬病病毒的能力。

This study was aimed at analyzing the inhibitory effects of remdesivir against RABV(CVS-11 and SC16)in vitro.Viral adsorption and replication,and direct killing effects were assayed with TCID_(50),DIFA and real-time PCR under different administration modes,with T705 as a reference drug.Remdesivir(500μmol/L),as compared with T705,significantly inhibited CVS-11 adsorption and replication in N2a or BHK-21 cells.The titer of viral mRNA significantly decreased in CVS-11 or SC16 infected N2a cells.However,no significant direct killing effect in CVS-11 or SC16 infected N2a cells was observed.Overall,our study demonstrated that remdesivir significantly blocks adsorption and inhibits replication of RABV after infection in vitro,but has no direct killing effect.