Journal
ANTIVIRAL RESEARCH
Volume 133, Issue -, Pages 140-144Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.antiviral.2016.08.003
Keywords
Newcastle disease virus; Raf kinase inhibitor V; Antivirals; Raf kinase
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Funding
- National Science Foundation of China [31402195, 31472195]
- Natural Science Foundation of Jilin Province [20140520171JH, 20160414029GH]
- Jilin University [4305050102TS, 450060501486, 430505010254]
- China Postdoctoral Science Foundation [2013M541313, 2016T90261]
- Chinese Special Fund for Agri-scientific Research in the public interest [201303033]
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Newcastle disease (ND) is still one of the major plagues of birds worldwide. Combat actions are limited to vaccines, highlighting the urgent need for new and amply available antiviral drugs. Previous results have shown that Newcastle disease virus (NDV) downregulates the intracellular Raf kinase inhibitor protein (RKIP) expression for efficient replication, suggesting that this molecular may be a suitable target for antiviral intervention. In the present work, we investigated whether or not the Raf kinase inhibitor V (RKIV), which functions in the same way as RKIP by targeting the intracellular Raf kinase, is able to suppress the propagation of enzootic virulent NDV in vitro and in vivo. In vitro antiviral activity of RKIV was assessed by cell-based assay, and in vivo activity was determined in the chicken model. Our results clearly showed that RKIV treatment protected the cells from NDV-induced CPE with the effective concentrations on nM level, and inhibited virus replication in the lungs of infected chickens in a dose dependent manner and protected chickens from the lethal infection by NDV. Thus, we conclude that the Raf kinase inhibitor compound RKIV, by inhibiting the host cellular target Raf kinase, might be very promising as a new class of antivirals against the enzootic virulent NDV infection. (C) 2016 Elsevier B.V. All rights reserved.
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