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Small Molecule Inhibitor of ATPase Activity of HSP70 as a Broad-Spectrum Inhibitor against Flavivirus Infections.
Yang, Jingjing; Xu, Yongfen; Yan, Yunzheng; Li, Wei; Zhao, Lei; Dai, Qingsong; Li, Yuexiang; Li, Song; Zhong, Jin; Cao, Ruiyuan; Zhong, Wu.
Afiliação
  • Yang J; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
  • Xu Y; CAS Key Laboratory of Molecular Virology and Immunology, Unit of Viral Hepatitis, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.
  • Yan Y; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
  • Li W; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
  • Zhao L; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
  • Dai Q; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
  • Li Y; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
  • Li S; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
  • Zhong J; CAS Key Laboratory of Molecular Virology and Immunology, Unit of Viral Hepatitis, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.
  • Cao R; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
  • Zhong W; National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
ACS Infect Dis ; 6(5): 832-843, 2020 05 08.
Article em En | MEDLINE | ID: mdl-31967789
Flaviviruses including Zika virus, Dengue virus, Japanese Encephalitis virus, and Yellow Fever virus cause heavy burdens to public health around the world. No specific antiviral drug is available in the clinic against these flavivirus infections. Heat-shock protein 70 (HSP70) has recently been proven to be a promising antiviral target against Zika virus and Dengue virus. Here, we report that Apoptozole, a small molecule inhibitor of ATPase activity of HSP70, has broad-spectrum anti-flavivirus potential. The mode of action analysis revealed that Apoptozole acted at the post-entry step. Transcriptome analysis revealed that genes related to cholesterol metabolism, fatty acid synthesis, and innate immunity were differentially expressed after treatment with Apoptozole. In vivo data suggested Apoptozole exerted protection effects against Zika virus (ZIKV) infection in a mouse model by enhancing the innate immune response, which suggested a novel anti-ZIKV mechanism of HSP70 inhibitors.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Benzamidas / Adenosina Trifosfatases / Proteínas de Choque Térmico HSP70 / Infecção por Zika virus / Imidazóis Limite: Animals Idioma: En Revista: ACS Infect Dis Ano de publicação: 2020 Tipo de documento: Article País de afiliação: China País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Benzamidas / Adenosina Trifosfatases / Proteínas de Choque Térmico HSP70 / Infecção por Zika virus / Imidazóis Limite: Animals Idioma: En Revista: ACS Infect Dis Ano de publicação: 2020 Tipo de documento: Article País de afiliação: China País de publicação: Estados Unidos