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Receptor tyrosine kinase inhibitors block proliferation of TGEV mainly through p38 mitogen-activated protein kinase pathways.
Dong, Wanyu; Xie, Wenting; Liu, Yunbo; Sui, Baokun; Zhang, Hao; Liu, Liran; Tan, Yubei; Tong, Xiaohan; Fu, Zhen F; Yin, Ping; Fang, Liurong; Peng, Guiqing.
Afiliação
  • Dong W; The State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, 430070, China; National Key Laboratory of Crop Gen
  • Xie W; The State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, 430070, China.
  • Liu Y; The State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, 430070, China.
  • Sui B; The State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, 430070, China.
  • Zhang H; The State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, 430070, China.
  • Liu L; The State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, 430070, China.
  • Tan Y; The State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, 430070, China.
  • Tong X; The State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, 430070, China.
  • Fu ZF; The State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, 430070, China; Departments of Pathology, College o
  • Yin P; National Key Laboratory of Crop Genetic Improvement, National Centre of Plant Gene Research, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China.
  • Fang L; The State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, 430070, China.
  • Peng G; The State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, 430070, China. Electronic address: penggq@mail.hza
Antiviral Res ; 173: 104651, 2020 01.
Article em En | MEDLINE | ID: mdl-31751591
ABSTRACT
Emerging coronaviruses (CoVs) primarily cause severe gastroenteric or respiratory diseases in humans and animals, and no approved therapeutics are currently available. Here, A9, a receptor tyrosine kinase inhibitor (RTKI) of the tyrphostin class, is identified as a robust inhibitor of transmissible gastroenteritis virus (TGEV) infection in cell-based assays. Moreover, A9 exhibited potent antiviral activity against the replication of various CoVs, including murine hepatitis virus (MHV), porcine epidemic diarrhea virus (PEDV) and feline infectious peritonitis virus (FIPV). We further performed a comparative phosphoproteomic analysis to investigate the mechanism of action of A9 against TGEV infection in vitro. We specifically identified p38 and JNK1, which are the downstream molecules of receptor tyrosine kinases (RTKs) required for efficient TGEV replication, as A9 targets through plaque assays, qRT-PCR and Western blotting assays. p38 and JNK1 inhibitors and RNA interference further showed that the inhibitory activity of A9 against TGEV infection was mainly mediated by the p38 mitogen-activated protein kinase (MAPK) signaling pathway. All these findings indicated that the RTKI A9 directly inhibits TGEV replication and that its inhibitory activity against TGEV replication mainly occurs by targeting p38, which provides vital clues to the design of novel drugs against CoVs.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Antivirais / Replicação Viral / Receptores Proteína Tirosina Quinases / Vírus da Gastroenterite Transmissível / Sistema de Sinalização das MAP Quinases / Inibidores de Proteínas Quinases / Interações Hospedeiro-Patógeno Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Antivirais / Replicação Viral / Receptores Proteína Tirosina Quinases / Vírus da Gastroenterite Transmissível / Sistema de Sinalização das MAP Quinases / Inibidores de Proteínas Quinases / Interações Hospedeiro-Patógeno Idioma: En Ano de publicação: 2020 Tipo de documento: Article