Isarubrolone C Promotes Autophagic Degradation of Virus Proteins via Activating ATG10S in HepG2 Cells.

Isarubrolone C is a bioactive polycyclic tropoloalkaloid from . Our previous study showed that isarubrolone C could trigger autophagy. Here, we report isarubrolone C potential in broad-spectrum antiviral effect and its antiviral mechanism . Our results show that isarubrolone C activated autophagy and reduced levels of viral proteins in the cells harboring HCV-CORE/NS5B, HBx, ZIKV-NS5, and HIV-RT, respectively. The role of isarubrolone C in suppression of the viral proteins was via an autophagic degradation pathway rather than a proteasome pathway. Co-immunoprecipitation assays revealed that isarubrolone C promoted both autophagy flux opening and the viral proteins being enwrapped in autolysosomes. PCR assays showed that isarubrolone C elevated the transcription levels of / and . Further, ATG10S high expression could efficiently enhance IL28A expression and the ability of isarubrolone C to degrade the viral proteins by promoting the colocalization of viral proteins with autolysosomes. Additionally, knockdown of endogenous caused both losses of the isarubrolone C antiviral effect and autolysosome formation. These results indicate that the role of isarubrolone C antiviruses is achieved by triggering the autophagic mechanism, which is mediated by endogenous ATG10S and IL28A activation. This is the first report about isarubrolone C potential of broad-spectrum antiviruses.