Cyclosporin A inhibits the replication of diverse coronaviruses

Cyclosporin A inhibits the replication of diverse coronaviruses
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DOI:
10.1099/vir.0.034983-0
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发表时间:
2011-11-01
影响因子:
3.8
通讯作者:
van Hemert, Martijn J.
van Hemert, Martijn J.
中科院分区:
医学3区
文献类型:
--
作者:
de Wilde, Adriaan H.;Zevenhoven-Dobbe, Jessika C.;van Hemert, Martijn J.

文献摘要

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低微摩尔,非细胞毒性浓度的环孢菌素A(CsA)强烈影响严重急性呼吸综合征冠状病毒(SARS-CoV),人冠状病毒229 E和小鼠肝炎病毒在细胞培养物中的复制,这是显而易见的,从GFP报告基因表达的强烈抑制和后代滴度高达4个对数的减少。在高多重性感染时,CsA治疗使SARS-CoV RNA和蛋白质合成几乎检测不到,表明复制早期阻断。siRNA介导的CsA主要靶点亲环素A和B表达的敲低并不影响SARS-CoV的复制,这表明这些特定的亲环素家族成员是不稳定的,或者降低的表达水平足以支持复制。
Low micromolar, non-cytotoxic concentrations of cyclosporin A (CsA) strongly affected the replication of severe acute respiratory syndrome coronavirus (SARS-CoV), human coronavirus 229E and mouse hepatitis virus in cell culture, as was evident from the strong inhibition of GFP reporter gene expression and a reduction of up to 4 logs in progeny titres. Upon high-multiplicity infection, CsA treatment rendered SARS-CoV RNA and protein synthesis almost undetectable, suggesting an early block in replication. siRNA-mediated knockdown of the expression of the prominent CsA targets cyclophilin A and B did not affect SARS-CoV replication, suggesting either that these specific cyclophilin family members are dispensable or that the reduced expression levels suffice to support replication.