A new coumarin derivative plays a role in rhabdoviral clearance by interfering glycoprotein function during the early stage of viral infection

Coumarin forms an elite class of naturally occurring compounds that possess promising antiviral therapeutic perspectives. In this study, a coumarin derivative 7-[6-(2-methylimidazole) hexyloxy] coumarin (D5) was designed and synthesized to evaluate antiviral activity on a rhabdovirus, spring viraemia of carp virus (SVCV). Our results demonstrated that D5 had a robust antiviral activity with > 90% inhibitory rate of SVCV expression in the host cells. And D5 significantly reduced viral-induced apoptosis and recovered virus-activated caspase-3/8/9 activities. Further data determined that SVCV could alter the cytoskeletal structure of EPC cells, characterized by a circumferential ring of microtubules and a disrupted microfilament organization, whereas cytoskeleton structure in D5-treated cells kept the normal morphology. Mechanistically speaking, D5 could interfere with SVCV replication inside or outside of cells through two different approaches. Before the process of virus entry into EPC cells, D5 had an impact on SVCV glycoprotein structure so as to disrupt viral binding to the cell surface or translocation to the cytosol. Another strategy for D5 to against SVCV was that D5 significantly suppressed SVCV-activated autophagy, which was beneficial for the host cells to restrict SVCV viral replication, accompanied by a higher phosphorylation of Akt-mTOR. In summary, our results revealed that D5 was effective in weakening SVCV infection and regulating SVCV-induced undesirable conditions, and this compound provided new therapeutic implications for the treatment of rhabdoviruses.