GS-441524体外对猪繁殖与呼吸综合征病毒的抑制效果

Inhibitory effect of GS-441524 on porcine reproductive and respiratory syndrome virus in vitro

利用CCK8方法测定GS-441524作用Marc-145细胞的安全浓度,并通过检测该化合物在病毒吸附、内化、核酸复制环节对病毒的感染能力、mRNA与蛋白合成能力的影响,评价了GS-441524体外抗猪繁殖与呼吸综合征病毒(porcine reproductive and respiratory syndrome virus,PRRSV)的活性,确定其在体外抑制PRRSV的作用阶段。结果显示,在Marc-145细胞中,GS-441524具有良好的抗PRRSV活性,其EC_(50)为2.65μmol/L;该化合物在体外显示出良好的安全性,其CC_(50)为2706.41μmol/L;对PRRSV复制周期的影响是GS-441524主要抑制PRRSV的复制早期阶段,而对病毒吸附、内化环节无阻断作用。结果表明,GS-441524具有抗PRRSV复制的潜在能力,该结果为抗PRRSV药物的选择和开发提供了新思路。

The aim of this study is to evaluate the potential anti-PRRSV effect of nucleoside analogue GS-441524 in vitro.In present study,the CCK8 method was used to determine the safe concentration of nucleoside analogue GS-441524 on Marc-145 cells,and the effects of this compound on virus infectivity,mRNA and protein synthesis in the process of virus adsorption,internalization,and nucleic acid replication were investigated.The anti-PRRSV activity,and the effect of nucleoside analogs GS-441524 on detailed stages of virus replication cycle in vitro were also evaluated.In Marc-145 cells,GS-441524 displayed good anti-PRRSV activity with an EC_(50) of 2.65μmol/L and presented good safety in vitro with a CC_(50) of 2706.41μmol/L.GS-441524 was demonstrated to mainly inhibit the PRRSV replication during the early stage of viral replication,while no blocking effect were revealed during the process of virus adsorption and internalization.The results of this study confirmed that GS-441524 had the potentiality of anti-PRRSV replication,which provide a new idea for the future selection and development of anti-PRRSV drugs.