Cyclosporin A inhibits the replication of diverse coronaviruses

被引:183
作者
de Wilde, Adriaan H. [1 ]
Zevenhoven-Dobbe, Jessika C. [1 ]
van der Meer, Yvonne [1 ]
Thiel, Volker [2 ,3 ]
Narayanan, Krishna [4 ]
Makino, Shinji [4 ]
Snijder, Eric J. [1 ]
van Hemert, Martijn J. [1 ]
机构
[1] Leiden Univ, Med Ctr, Ctr Infect Dis, Mol Virol Lab,Dept Med Microbiol, Leiden, Netherlands
[2] Kantonal Hosp St Gallen, Inst Immunobiol, St Gallen, Switzerland
[3] Univ Zurich, Vetsuisse Fac, Zurich, Switzerland
[4] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX USA
基金
瑞士国家科学基金会;
关键词
C VIRUS-REPLICATION; RESPIRATORY SYNDROME CORONAVIRUS; HEPATITIS-C; POTENT INHIBITOR; CYCLOPHILIN; CHLOROQUINE; DEBIO-025; INFECTION; PROTEIN;
D O I
10.1099/vir.0.034983-0
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
引用
收藏
页码:2542 / 2548
页数:7
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