title: Moroxydine hydrochloride inhibits grass carp reovirus replication and suppresses apoptosis in Ctenopharyngodon idella kidney cells.
abstract: Moroxydine hydrochloride (Mor) is known to have multi-antiviral activities against DNA and RNA viruses but very little information exists on its pharmacology. The paper was undertaken to explore the antiviral response and antiapoptotic mechanism of Mor against grass carp reovirus (GCRV) in Ctenopharyngodon idella kidney (CIK) cells. The results showed that exposing GCRV-infected cell to 6.3 μg mL(-1) of Mor for 96 h avoid ca. 50% apoptosis. Meanwhile, Mor had lower cytotoxicity than ribavirin (Rib) as the value of safe concentration was threefold higher than effective concentration and the compound could ensure sufficient into and out of cells within 4 h when tested at the maximal safe concentration. Mor blocked the GCRV-induced cytopathic effects and eliminated nucleocapsids in CIK cells to keep the normal morphological structure. Moreover, the expressions of viral protein genes were significantly inhibited especially the guanylyl transferase and RNA-dependent RNA polymerase related expression. Furthermore, GCRV caused Bcl-2 down-regulation and Bax mitochondrial translocation was prevented by treatment of CIK cells with Mor. The downstream effector, caspase activity was also significantly inhibited in Mor treated cells. The potential mechanism might be that mitochondrial apoptotic signals were not activated by the intervention of Mor for targeting viral gene expression. Taken together, Mor showed high anti-GCRV activity and had been proved as a secure and promising agent in viral controlling in aquaculture industry.
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Yu
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Chen
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Ling
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Hao
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address: wanggaoxue@126.com.
authors.forename: Gao-Xue
authors.initials: GX
authors.lastname: Wang
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address: zhubin1227@126.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D017756:Aquaculture; D001645:Biguanides; D002347:Carps / Q000033:anatomy & histology / Q000821:virology*; D061945:Caspase Inhibitors / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D003001:Cloning, Molecular; D004261:DNA Replication / Q000187:drug effects; D015536:Down-Regulation; D015870:Gene Expression / Q000187:drug effects; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000821:virology; D009025:Morpholines / Q000494:pharmacology* / Q000633:toxicity; D010802:Phylogeny; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics / Q000378:metabolism; D012087:Reoviridae / Q000187:drug effects*; D012088:Reoviridae Infections / Q000662:veterinary / Q000821:virology; D012254:Ribavirin / Q000494:pharmacology / Q000633:toxicity; D017422:Sequence Analysis, DNA; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D001645:Biguanides; D061945:Caspase Inhibitors; D009025:Morpholines; D012254:Ribavirin; D012324:RNA-Dependent RNA Polymerase; D020169:Caspases; C005267:moroxydine
keywords: Apoptosis; CIK cell; Grass carp reovirus; Moroxydine hydrochloride