Small Molecule Inhibitor of ATPase Activity of HSP70 as a Broad-Spectrum Inhibitor against Flavivirus Infections.,ACS Infectious Diseases

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Small Molecule Inhibitor of ATPase Activity of HSP70 as a Broad-Spectrum Inhibitor against Flavivirus Infections.
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2020-02-03 , DOI: 10.1021/acsinfecdis.9b00376
Jingjing Yang ₁ , Yongfen Xu ₂ , Yunzheng Yan ₁ , Wei Li ₁ , Lei Zhao ₁ , Qingsong Dai ₁ , Yuexiang Li ₁ , Song Li ₁ , Jin Zhong ₂ , Ruiyuan Cao ₁ , Wu Zhong ₁

Affiliation

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.

中文翻译：

HSP70 ATP酶活性的小分子抑制剂，作为抗黄病毒感染的广谱抑制剂。

包括寨卡病毒，登革热病毒，日本脑炎病毒和黄热病病毒在内的黄病毒对世界各地的公共卫生造成沉重负担。临床上没有针对这些黄病毒感染的抗病毒药物。热激蛋白70（HSP70）最近被证明是针对Zika病毒和登革热病毒的有希望的抗病毒靶标。在这里，我们报道Apoptozole，HSP70的ATPase活性的小分子抑制剂，具有广谱抗黄病毒的潜力。作用模式分析表明，Apoptozole在进入后步骤起作用。转录组分析显示，与Apoptozole治疗后，与胆固醇代谢，脂肪酸合成和先天免疫相关的基因差异表达。

更新日期：2020-01-22

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