Small Molecule Inhibitor of ATPase Activity of HSP70 as a Broad-Spectrum Inhibitor against Flavivirus Infections.
Jingjing YangYongfen XuYunzheng YanWei LiLei ZhaoQingsong DaiYuexiang LiSong LiJin ZhongRuiyuan CaoXinbo ZhouPublished in: ACS infectious diseases (2020)
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.
Keyphrases
- zika virus
- heat shock protein
- dengue virus
- small molecule
- immune response
- heat shock
- public health
- aedes aegypti
- mouse model
- fatty acid
- protein protein
- single cell
- heat stress
- primary care
- toll like receptor
- electronic health record
- dendritic cells
- endoplasmic reticulum
- gene expression
- climate change
- big data
- machine learning
- artificial intelligence
- drug induced
- human health
- adverse drug
- risk assessment
- low density lipoprotein
- global health
- bioinformatics analysis