ReferenceID 590
Saikosaponin D suppresses enterovirus A71 infection by inhibiting autophagy
Signal Transduct Target Ther
The dysregulation of autophagy, an evolutionarily conserved lysosomal degradation process, has been implicated in a wide variety of human diseases, and thus, small chemicals that modulate autophagy have therapeutic poten
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Record Fields
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- Reference Id
- 590
- Evidence Id
- 17180
- Core Evidence Id
- 17180
- Source Reference Id
- 1168
- Herb2 Reference Id
- HBREF001959
- Subject Paper Key
- HBIN042801_30820356
- Pubmed Id
- 30820356
- Doi
- 10.1038/s41392-019-0037-x
- Paper Title
- Saikosaponin D suppresses enterovirus A71 infection by inhibiting autophagy
- Paper Abstract
- The dysregulation of autophagy, an evolutionarily conserved lysosomal degradation process, has been implicated in a wide variety of human diseases, and thus, small chemicals that modulate autophagy have therapeutic potential. Here, we assessed the ability of active components isolated from Bupleurum falcatum, a popular Chinese herb, to modulate autophagy. We found that saikosaponin D (SsD) and A (SsA) but not C (SsC) potently and reversibly inhibited the fusion of autophagosomes and lysosomes, resulting in the accumulation of autophagosomes, an increased lysosomal pH, and TFEB nuclear translocation. RAB5A knockdown or the expression of a dominant-negative RAB5 mutant significantly reduced the ability of SsD or SsA to block autophagy. Enterovirus A71 (EV-A71), the cause of hand-foot-mouth disease, has been shown to induce autophagy. We found that SsD potently inhibited EV-A71 RNA replication and subsequent viral protein synthesis, thereby preventing EV-A71-induced cell death. ATG5 knockdown inhibited EV-A71 viral protein synthesis, whereas autophagy induction by rapamycin promoted synthesis. Taken together, our data indicate that SsD and SsA are potent late-stage autophagy inhibitors that can be used to prevent EV-A71 infection.
- Journal
- Signal Transduct Target Ther
- Publish Year
- 2019
- Experiment Subject
- autophagy
- Experiment Type
- Cell Experiment
- Phenotype Related
- Hand-foot-mouth Disease; Ev-a71 Infection
- Paper Title Cn
- Paper Title En
- Saikosaponin D suppresses enterovirus A71 infection by inhibiting autophagy
- Bilingual Status
- semi_complete