控制溶瘤腺病毒YSCH-01复制的抗病毒药物筛选探究

Screening of Antiviral Drugs to Control the Replication of Oncolytic Adenovirus YSCH-01

该文目的是通过体外实验筛选能够有效抑制重组溶瘤腺病毒YSCH-01复制的药物,为该产品的临床安全使用提供指导。首先,选取了文献中常见的5种潜在可以抑制腺病毒的药物,采用细胞计数试剂盒(cell counting kit-8,CCK-8)杀伤实验测试了这5种药物对人源细胞的自身毒性,排除了细胞毒性最强的赛度替尼。然后,采用结晶紫染色法检测了剩余4种药物对YSCH-01病毒杀伤细胞能力的抑制效果。同时,测定了这4种药物对YSCH-01病毒复制能力的抑制效果。结果显示,西多福韦和司他夫定显著地降低YSCH-01病毒的复制和杀伤能力,更昔洛韦次之。最后,进一步确定了西多福韦和司他夫定对YSCH-01病毒的半数抑制浓度,计算出这2种药物的安全指数(safety index,SI)值。上述研究表明,西多福韦和司他夫定对人源细胞不良影响小,对溶瘤腺病毒YSCH-01抑制能力强,可作为溶瘤腺病毒YSCH-01在临床应用中的安全备用药物。

The purpose of this article is to select the drugs which can effectively inhibit the recombinant oncolytic adenovirus YSCH-01 replication through in vitro experiments,to provide guidance for ensuring safety use of adenovirus products in clinical.First,five drugs commonly reported in the literature with potential to inhibit adenovirus were selected.The toxicity of these five drugs on human cells was tested by CCK-8(cell counting kit-8)and Cedutinib,the most cytotoxic drug,was excluded.Then,crystal violet staining was used to detect the inhibitory effect of the remaining four drugs on YSCH-01 killing ability.At the same time,the inhibitory effect of these 4 drugs on YSCH-01 replication was measured.The results showed that Cidofovir and Stavudine significantly inhibited the replication and killing ability of YSCH-01,followed by Ganciclovir.Further,the half inhibitory concentrations of Cidofovir and Stavudine against YSCH-01 were determined and the SI values of the two drugs were calculated.This study showed that Cidofovir and Stavudine had little adverse effect on human cells but shown strong inhibition against adenovirus YSCH-01,which could be used as standby safe drugs for clinical application of adenovirus YSCH-01.