title: SP600125 inhibits Orthopoxviruses replication in a JNK1/2 -independent manner: Implication as a potential antipoxviral.
abstract: The pharmacological inhibitor SP600125 [anthra(1,9-cd)pyrazol-6(2H)-one 1,9-pyrazoloanthrone] has been largely employed as a c-JUN N-terminal kinase (JNK1/2) inhibitor. In this study, we evaluated whether pretreatment with SP600125 was able to prevent Orthopoxviruses Vaccinia virus (VACV), Cowpox virus (CPXV) and modified Vaccinia virus Ankara (MVA) replication. We found that incubation with SP600125 not only blocked virus-stimulated JNK phosphorylation, but also, significantly reduced virus production. We observed 1-3 log decline in viral yield depending on the cell line infected (A31, BSC-40 or BHK-21). The reduction in viral yield correlated with a dramatic impact on virus morphogenesis progress, intracellular mature viruses (IMV) were barely detected. Despite the fact that SP600125 can act as an efficient anti-orthopoxviral compound, we also provide evidence that this antiviral effect is not specifically exerted through JNK1/2 inhibition. This conclusion is supported by the fact that viral titers measured after infections of JNK1/2 knockout cells were not altered as compared to those of wild-type cells. In contrast, a decline in viral titers was verified when the infection of KO cells was carried out in the presence of the pharmacological inhibitor. SP600125 has been the focus of recent studies that have evaluated its action on diverse viral infections including DNA viruses. Our data support the notion that SP600125 can be regarded as a potential antipoxviral compound.
authors: Grupo de Transdução de Sinal/Orthopoxvirus, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil.
authors: Anna C T C
authors: AC
authors: Pereira
authors: Jamária A P
authors: JA
authors: Soares-Martins
authors: Flávia G G
authors: FG
authors: Leite
authors: André F P
authors: AF
authors: Da Cruz
authors: Alice A
authors: AA
authors: Torres
authors: Thais
authors: T
authors: Souto-Padrón
authors: Erna G
authors: EG
authors: Kroon
authors: Paulo C P
authors: PC
authors: Ferreira
authors: Cláudio A
authors: CA
authors: Bonjardim
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism*; D041681:NIH 3T3 Cells; D018155:Orthopoxvirus / Q000187:drug effects* / Q000648:ultrastructure; D010766:Phosphorylation; D011213:Poxviridae Infections / Q000378:metabolism; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000873:Anthracenes; D000998:Antiviral Agents; C432165:pyrazolanthrone; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8