Efficient antiviral activity of a novel magnolol derivative against aquatic rhabdoviruses

Micropterus salmoides rhabdovirus (MSRV) is a prominent pathogen that mainly endangers largemouth bass fry, which often causes devastating diseases to largemouth bass and leads to huge economic losses in aquaculture. So far, there is no approved effective measure to control MSRV infection. In the study, 24 magnolol derivatives were used to conduct anti-MSRV activity screening by RT-qPCR, and the results indicated that 5,5′-diallyl-3,3′-dinitro-[1,1′-biphenyl]-2,2′-diol (M3) exhibited the best anti-MSRV efficiency with IC 50 of 0.92 μM. Moreover, further study showed that the CPE induced by MSRV was obviously weaken by M3, and the viral titers were also significantly decreased by M3 within 96 h after MSRV infection ( p < 0.05). Next, the anti-MSRV mechanism of M3 was preliminarily investigated, and the findings illustrated that M3 did not directly act on MSRV virion which had no effect on the infectivity of MSRV. Furthermore, the adsorption of MSRV onto GCO cells was not hindered by M3. The results of cell cycle detected by flow cytometry demonstrated that M3 altered the state of cell cycle arrest in S phase induced by MSRV, influencing the environment required for virus replication. In addition, observation of survival rate and determination of viral load were conducted to further verify the antiviral activity of M3 against MSRV. The results illustrated that administration with M3 at the dose of 20 mg/kg via intraperitoneal injection significantly enhanced the survival rate of largemouth bass infected with MSRV by 35.98 % ( p < 0.01). Moreover, the viral loads of liver, spleen and kidney were significantly decreased by M3 on day 3 and day 5 post MSRV infection ( p < 0.05). Finally, the antiviral effects of M3 against aquatic rhabdoviruses spring viremia of carp virus (SVCV) and infectious hematopoietic necrosis virus (IHNV) were explored, and the results demonstrated that M3 evidently lessened the production of CPE induced by SVCV and IHNV, and inhibited the proliferation of SVCV and IHNV in EPC cells in a dose-dependent manner, with IC 50 of 2.92 μM and 2.78 μM, respectively. To sum up, M3 exhibits a high antiviral activity against MSRV, and is expected to be developed into antiviral specific drugs against rhabdoviruses in aquaculture. • M3, a magnolol derivative, showed potent anti-MSRV activity, demonstrating potential as a highly-effective therapeutic agent. • M3 inhibited the replication of MSRV by changing S-phase arrest induced by MSRV and disrupting viral replication environment. • M3 significantly improved survival of MSRV-infected largemouth bass, protecting more fish from death of MSRV infection. • M3 inhibited SVCV and IHNV replication in EPC cells, showing broad-spectrum antiviral activity against aquatic rhabdoviruses.