Intriguingly, we revealed that Hc-CATH decreased the susceptibility of host cells to ZIKV by downregulating expression of AXL, a TAM (TYRO3, AXL and MERTK) family kinase receptor that mediates ZIKV infection, and subsequently reversed the negative regulation of AXL on host’s type I interferon response. Here, AXL is linked to Zika virus infectious disease.