title: A Raf kinase inhibitor demonstrates antiviral activities both in vitro and in vivo against different genotypes of virulent Newcastle disease virus.
abstract: 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.
authors: Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Jilin University, Xi'an Road 5333, Changchun, Jilin 130062, China. Electronic address: yin@jlu.edu.cn.
authors: Renfu
authors: R
authors: Yin
authors: College of Food Science and Engineering, Jilin University, Xi'an Road 5333, Changchun, Jilin 130062, China.
authors: Xinxin
authors: X
authors: Liu
authors: Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Jilin University, Xi'an Road 5333, Changchun, Jilin 130062, China.
authors: Pingze
authors: P
authors: Zhang
authors: Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Jilin University, Xi'an Road 5333, Changchun, Jilin 130062, China.
authors: Yanyu
authors: Y
authors: Chen
authors: Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Jilin University, Xi'an Road 5333, Changchun, Jilin 130062, China.
authors: Guangyao
authors: G
authors: Xie
authors: Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Jilin University, Xi'an Road 5333, Changchun, Jilin 130062, China.
authors: Lili
authors: L
authors: Ai
authors: Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Jilin University, Xi'an Road 5333, Changchun, Jilin 130062, China.
authors: Cong
authors: C
authors: Xue
authors: Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Jilin University, Xi'an Road 5333, Changchun, Jilin 130062, China.
authors: Jing
authors: J
authors: Qian
authors: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors: Yuhai
authors: Y
authors: Bi
authors: CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Hubei, China.
authors: Jianjun
authors: J
authors: Chen
authors: China Animal Health and Epidemiology Center, Qingdao, Nanjing Road 369, Qingdao, Shandong 266032, China.
authors: Yuzhang
authors: Y
authors: Sun
authors: Comprehensive Pneumology Center, Institute of Lung Biology and Disease (iLBD), Helmholtz Zentrum Muenchen, Ingolstaedter Landstrasse 1, D-85764 Neuherberg/Munich, Germany.
authors: Tobias
authors: T
authors: Stoeger
authors: Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Jilin University, Xi'an Road 5333, Changchun, Jilin 130062, China. Electronic address: dingzhuang@jlu.edu.cn.
authors: Zhuang
authors: Z
authors: Ding
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D009521:Newcastle Disease / Q000188:drug therapy / Q000821:virology; D009522:Newcastle disease virus / Q000187:drug effects* / Q000235:genetics* / Q000472:pathogenicity; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D048491:Proto-Oncogene Proteins A-raf / Q000037:antagonists & inhibitors*; D014774:Virulence
chemical_list: D000998:Antiviral Agents; D047428:Protein Kinase Inhibitors; D048491:Proto-Oncogene Proteins A-raf
keywords: Antivirals; Newcastle disease virus; Raf kinase; Raf kinase inhibitor V