Evaluation on antiviral activity of coumarin derivatives against spring viraemia of carp virus in epithelioma papulosum cyprini cells
As one of the most serious pathogens in the freshwater aquatic environment, spring viraemia of carp virus (SVCV) induces a high mortality rate in several cyprinid fishes. In this study, we designed and synthesized a total of 44 coumarin derivatives to evaluate the anti-SVCV activity. By comparing the inhibitory concentration at half-maximal activity (IC50), two imidazole coumarins (B4 and C2) were selected, with maximum inhibitory rates on SVCV more than 90%. Mechanistically, B4 or C2 did not affect viral adhesion and delivery from endosomes to the cytosol. Further, B4 and C2 could decline the apoptosis in SVCV-infected cells and the viral activated caspase-3, 8, 9 activities. Other results showed that SVCV induced the cytoskeletal structure to be a circumferential ring of microtubules near the nucleus, with occurring a disrupted microfilament organization. In comparison, cytoskeleton structure in drug-treated cells kept complete. In addition, the cellular microstructure in drug treatments showed no significant change; while SVCV-infected cells were seriously shrunk, and observed typical apoptotic features including cell shrinkage, volume reduction and cell blebbing. More importantly, B4 and C2 enhanced anti-oxidative enzyme gene expression and triggered the Nrf-2 pathway to keep balance of intracellular redox state. Therefore, the use of two imidazole coumarins (B4 and C2) could be a viable way of preventing and controlling SVCV infection.Graphical abstract
Two imidazole coumarins inhibit SVCV replication in host cells by activating the Nrf-2 pathway to keep balance of intracellular redox state, and they could be a potential viable way of preventing and controlling SVCV infection.