Immune responses and protective efficacy on 4-(2-methoxyphenyl)-3,4-dihydro-2H-chromeno[4,3-d] pyrimidine-2,5 (1H)-dione against spring viremia of carp virus in vivo

Abstract

Spring viremia of carp virus (SVCV) is a highly pathogenic sprivivirus that continues to cause outbreaks in cyprinidae characterized by high mortality. Currently, few therapeutics have approved for use in aquaculture against SVCV infection. Previously, we reported that 4-(2-methoxyphenyl)-3,4-dihydro-2H-chromeno[4,3-d] pyrimidine-2,5(1H)-dione-phenylpropanoid (S3) inhibits SVCV proliferation. It was first appeared in the S5 series of compounds. Compared with S5, S3 is easier to synthesize and has a higher yield. Here, in order to further evaluate the practical application potential of S3 in aquaculture, common carp as a model organism was carried out relevant experiments. In this study, we evaluated toxicity of S3 in vivo. The results showed that the dose below 100 μg/mL is safe, and there was a significant toxicity if it exceeds this dose. In pathogenicity tested of SVCV, the 50% lethal dose (LD50) of the present SVCV isolate to present common carp was approximately 101.6-fold TCID50/fish. Subsequently, further data suggested that S3 was stability with a prolonged inhibitory half-life in the early stage of virus infection (1–4 days). Importantly, intraperitoneal (i.p.) therapy of S3 markedly decreased fish mortality and reduced virus copies in both spleen and kidney. Mechanically, S3 enhanced the levels of IFN-related genes demonstrated that S3 indirectly activated IFNs for the clearance of SVCV in common carp. Additionally, the results of HE staining showed that S3 may be able to attenuate inflammation symptoms in SVCV infected fish. Therefore, the phenylpropanoid derivative S3 has potential to be used as an anti-SVCV therapeutics against fish viral diseases.