期刊
VIRUS RESEARCH
卷 184, 期 -, 页码 44-53出版社
ELSEVIER
DOI: 10.1016/j.virusres.2014.02.010
关键词
HCoV-NL63; Cyclosporine/FK506-non-immunosuppressive derivatives; Inhibition of viral replication; Cyclophilin A; FKBP
类别
资金
- German Government (Zoonosis Network, Consortium on ecology and pathogenesis of SARS) [01KI1005]
Until recently, there were no effective drugs available blocking coronavirus (Coy) infection in humans and animals. We have shown before that CsA and FK506 inhibit coronavirus replication (Carbajo-Lozoya, J., Muller, M.A., Kallies, S., Thiel, V., Drosten, C., von Brunn, A. Replication of human coronaviruses SARS-CoV, HCoV-NL63 and HCoV-229E is inhibited by the drug FK506. Virus Res. 2012; Pfefferle, S., Schopf, J., Kogl., M., Friedel, C., Muller, M.A., Stellberger, T., von Dall'Armi, E., Herzog, P., Kallies, S., Niemeyer, D., Ditt, V., Kuri, T., Zust, R., Schwarz, F., Zimmer, R., Steffen, I., Weber, F., Thiel, V., Herrler, G., Thiel, H.-J., Schwegmann-WeBels, C., Pohlmann, S., Haas, J., Drosten, C. and von Brunn, A. The SARS-Coronavirus-host interactome: identification of cyclophilins as target for pan-Coronavirus inhibitors. PLoS Pathog., 2011). Here we demonstrate that CsD Alisporivir, NIM811 as well as novel non-immunosuppressive derivatives of CsA and FK506 strongly inhibit the growth of human coronavirus HCoV-NL63 at low micromolar, non-cytotoxic concentrations in cell culture. We show by qPCR analysis that virus replication is diminished up to four orders of magnitude to background levels. Knockdown of the cellular Cyclophilin A (CypA/PPIA) gene in Caco-2 cells prevents replication of HCoV-NL63, suggesting that CypA is required for virus replication. Collectively, our results uncover Cyclophilin A as a host target for CoV infection and provide new strategies for urgently needed therapeutic approaches. (C) 2014 Elsevier B.V. All rights reserved.
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