Viruses-Basel
·
2022
·Vol. 14
·期 7
·1421
·
IF 5.818
Yingjie Jin,Fei Yang,Gengrong Zhang,Qing Yu,Gaoxue Wang,Fei Ling,Tianqiang Liu
Micropterus salmoidesrhabdovirus (MSRV) is a primary viral pathogen in largemouth bass aquaculture, which leads to tremendous economic losses yearly. Currently, there are no approved drugs for the treatment and control of this virus. Our previous studies screened the herbMagnolia officinalisfrom many traditional Chinese medicines, and we isolated and identified magnolol as its main active compound against multiple rhabdoviruses, including MSRV. On the basis of the structure–activity relationship and pharmacophore model of magnolol, two new magnolol derivatives, namely, hydrogenated magnolol and 2,2′-dimethoxy-magnolol, were designed and synthesized. Their anti-MSRV activities were systematically investigated both in vitro and in vivo. By comparing the half-maximal inhibitory concentration (IC50), it was found that hydrogenated magnolol possessed a higher anti-MSRV activity than magnolol and 2,2′-dimethoxy-magnolol, with an IC50of 13.37 μM. Furthermore, hydrogenated magnolol exhibited a protective effect on the grass carp ovary (GCO) cell line by reducing the cytopathic effect induced by MSRV. Further studies revealed that hydrogenated magnolol did not directly impact virions or interfere with MSRV adsorption. It worked within the 6–8 h of the phase of virus replication. In vivo treatment of MSRV infection with magnolol and hydrogenated magnolol showed that they significantly improved the survival rate by 44.6% and 62.7%, respectively, compared to MSRV-infected groups. The viral load measured by the expression of viral glycoprotein in the organs including the liver, spleen, and kidney also significantly decreased when fish were intraperitoneally injected at a dose of 20 mg/kg. Altogether, the structural optimization of magnolol via hydrogenation of the propylene groups increased its anti-MSRV activity both in vitro and in vivo. These results may provide a valuable reference for anti-MSRV drug discovery and development in aquaculture.Keywords:Micropterus salmoidesrhabdovirus (MSRV);magnolol;largemouth bass;antiviral activity
研究领域:
水产养殖学
·
病毒学
·
药物化学
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DOI
PubMed
高影响因子
AQUACULTURE
·
2022
·
IF 5.135
Yang Hu,Huan Wang,Lei Liu,Jia-yun Yao,Jiong Chen
Micropterus salmoides rhabdovirus (MSRV) is a fish viral pathogen that causes severe disease and huge economic losses in the largemouth bass (M. salmoides ) farming industry in aquaculture. Currently, there is no treatment strategy for MSRV. Thus, anti-MSRV drugs are urgently needed. In this study, it was found that the ethanol extract of Arctium lappa L. had good anti-MSRV activity, and the inhibition rate of G and N protein expression of MSRV was >95%. Further studies showed that arctigenin, a natural component of A. lappa L., could inhibit MSRV infection in a dose-dependent mode on grass carp ovary (GCO) cells. In addition, arctigenin could effectively inhibit the cytopathic changes caused by virus and significantly reduce the titer of virus. The pretreatment and post-treatment experiments showed that arctigenin had preventive and therapeutic effects on MSRV infection. TOA and TOR studies indicated that arctigenin may play an antiviral role in the early stage of virus replication. Interestingly, we found that arctigenin treatment significantly inhibited mitochondrial damage in GCO cells by preserving mitochondrial function and maintaining mitochondrial membrane potential levels (ΔΨm). More importantly, arctigenin was also effective against MSRV infection in largemouth bass. The survival rate of infected fish was increased by 16% and 20% respectively by adding 0.5% and 1% arctigenin in the diet. Additionally, the virus titer of the largemouth bass in the arctigenin treatment group was significantly decreased. In summary, arctigenin is confirmed to be a natural product with the excellent anti-MSRV activity, and its application in the treatment of MSRV is promising in aquaculture.
研究领域:
水产养殖
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病毒学
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药理学
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分子生物学
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产品关联
DOI
高影响因子
AQUACULTURE
·
2022
·
IF 5.135
Linhan Li,Tao Zhang,Gengrong Zhang,Guoqing Zhou,Fei Yang,Erlong Wang,Tianqiang Liu,Gaoxue Wang
Micropterus salmoides rhabdovirus (MSRV) seriously threats largemouth bass farming in China. Vaccine is a widely-used way to protect against virus infection. However, traditional intramuscular injection is inconvenient, time-consuming, and hard to applicate universally. We employed the naturally biodegradable bacterial nanocellulose (BNC) as effective virus antigen carriers for bath vaccination and improving the largemouth bass immune response. In this study, 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-mediated oxidation of bacterial cellulose (BC) was applied to produce carboxylated BC, which was validated by Fourier transform infrared spectroscopy (FTIR) and elementary analysis. Followed by a controlled sulfuric acid hydrolysis reaction to form carboxylated bacterial nanocellulose (BNC-COOH) with an average size of about 350 nm. Amination reaction was conducted via conjugating the amine groups in MSRV glycoproteins (G) with the carboxyl groups in the BNC-COOH. The prepared bacterial nanocellulose loaded glycoprotein complex (BNCs-G) was used to vaccine largemouth bass via bath immunization. The protective effects were assessed by analyzing MSRV G proteins-specific serum antibody levels and the expression of four immune-related genes ( IgM , IL-12 , TCR , TNF- α, and CD4 ). Results showed that serum antibody levels and the expression of immune-related genes were significantly increased for BNCs-G bath-vaccinated groups (40 mg L −1 ), compared with PBS and the naked G protein groups. After bath immunization for four weeks, fish were challenged with a lethal dose of MSRV. The survival rates for control group (PBS), BNCs group (40 mg L −1 ), the naked G protein groups (40 mg L −1 ) and three BNCs-G groups (10 mg L −1 , 20 mg L −1 and 40 mg L −1 ) were 0%, 0%, 30.0%, 16.7%, 46.7% and 66.7%, respectively. These results indicated that BNCs could be a plausible candidate for the vaccine carrier system, and the BNC loaded glycoprotein showed good immunogenicity.
研究领域:
水产养殖
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免疫学
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病毒学
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纳米技术
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生物医学工程
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产品关联
DOI
高影响因子
JOURNAL OF FISH DISEASES
·
2022
·Vol. 45
·期 6
·895-905
·
IF 2.58
Bo-Yang Li,Fei Yang,Zhong-Yu Zhang,Yu-Feng Shen,Tao Wang,Liang Zhao,Jia-Cheng Qin,Fei Ling,Gao-Xue Wang
Micropterus salmoides rhabdovirus (MSRV) is an significant pathogen that causes high mortality and related economic losses in bass aquaculture. There is no effective or approved therapy to date. In this study, we evaluated the anti-MSRV effects of 22 quinoline derivatives in grass carp ovary (GCO) cells. Among these compounds, 8-hydroxyquinoline exhibited valid inhibition in decreasing MSRV nucleoprotein gene expression levels of 99.3% with a half-maximal inhibitory concentrations (IC 50 ) value of 4.66 μM at 48 h. Moreover, 8-hydroxyquinoline significantly enhanced a protective effect in GCO cells by reducing the cytopathic effect (CPE). By comparing the anti-MSRV activity of 22 quinoline derivatives, we found that 8-hydroxyquinoline possessed the efficient active site of 8-hydroxyl and inhibited MSRV infection in vitro. For in vivo studies, 8-hydroxyquinoline via intraperitoneal injection exhibited an antiviral effect in MSRV-infected largemouth bass by substantially enhancing the survival rate by 15.0%. Importantly, the viral loads in the infected largemouth bass notably reduced in the spleen on the third days post-infection. Overall, 8-hydroxyquinoline was considered to be an efficient agent against MSRV in aquaculture.
研究领域:
水产养殖
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病毒学
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药理学
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产品关联
DOI
PubMed
高影响因子
AQUACULTURE
·
2025
·
IF 3.9
Fei Yang,Zhiqiang Zhang,Shenye Qu,Gaoxue Wang,Qing Yu,Fei Ling
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.
研究领域:
水产养殖学
·
病毒学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
VIRUS RESEARCH
·
2022
·
IF 6.286
Bo-Yang Li,Jia-Cheng Qin,Yu-Feng Shen,Fei Yang,Tao Wang,Fei Ling,Gao-Xue Wang
Micropterus salmoides rhabdovirus (MSRV) has a high mortality rate and causes huge economic losses to the aquaculture industry. In this study, we identified that ursolic acid (UA) had antiviral efficacy against MSRV in vitro and in vivo . The results showed that UA inhibited MSRV replication in grass carp ovary (GCO) cells with a half-maximal inhibitory concentration (IC 50 ) of 5.55 μM, reduced viral titers and decreased cytopathic effects (CPE). Mechanistically, UA does not directly damage viral particles. On the other hand, UA inhibits MSRV replication by altering viral binding and release. Furthermore, pre- and post-treatment assays revealed that UA had preventive and therapeutic effects. For in vivo studies, UA could enhance the survival rate of MSRV-infected largemouth bass. Similarly, UA reduced the viral load of MSRV in the heart, spleen and brain at 3, 5 and 7 d post-infection. In conclusion, UA is an effective inhibitor of rhabdovirus in aquaculture.
研究领域:
水产养殖学
·
病毒学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF FISH DISEASES
·
2026
·
IF 2.3
Qianhao Shao,Yan Zhou,Xinhui Tong,Huan Qi,Shiwen Sun,Xutin Guan,Jidong Wang,Dawei Song
The highly pathogenic Micropterus salmoides rhabdovirus (MSRV) poses a serious threat to largemouth bass aquaculture, leading to considerable economic losses. We assessed the anti-MSRV activity of milbemycin A4 (A4), a macrolide derived from Streptomyces bingchenggensis in both cell-based and animal models. Cytotoxicity assays revealed that A4 was not toxic to EPC cells at concentrations up to 6.4 mg/L. It significantly reduced viral N gene expression by approximately 90.25%. A4 also suppressed MSRV-induced apoptosis, decreasing the apoptotic cell population by about 21.88%, and preserved mitochondrial membrane potential. Investigations of the viral life cycle demonstrated that A4 directly targets virions, impairing their binding and internalization, and additionally inhibits early post-entry replication events. In vivo analyses further revealed that A4 treatment led to significant induction of antiviral-related genes ( IRF3 , IRF7 and IFN-γ ), which was accompanied by enhanced survival of infected fish (54%), along with reduced viral accumulation in the liver and spleen and alleviated histopathological damage. These findings suggest that A4 exhibits strong anti-MSRV activity by targeting early infection stages, protecting mitochondrial integrity and enhancing host innate immunity, highlighting its potential for application in aquaculture disease control.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF FISH DISEASES
·
2024
·Vol. 47
·期 4
·e13915
·
IF 2.2
Fei Yang,Bin Yang,Kaige Song,Yingjie Jin,Gaoxue Wang,Pengfei Li,Qing Yu,Fei Ling
Micropterus salmoides rhabdovirus (MSRV) is a formidable pathogen, presenting a grave menace to juvenile largemouth bass. This viral infection frequently leads to epidemic outbreaks, resulting in substantial economic losses within the aquaculture industry. Unfortunately, at present, there are no commercially available vaccines or pharmaceutical treatments to combat this threat. In order to address the urgent need for therapeutic strategy to resist MSRV infection, the antiviral activity of natural product honokiol against MSRV was explored in this study. Firstly, cellular morphology was directly observed in an inverted microscope when treated with honokiol after MSRV infection. The results clarified that honokiol significantly lessened cytopathic effect (CPE) induced by MSRV and protected the integrity of GCO cells. Furthermore, the viral nucleic acid expression (G gene) was detected by reverse transcription real-time quantitative PCR (RT-qPCR) and the results indicated that honokiol significantly decreased the viral loads of MSRV in a concentration-dependent manner, and honokiol showed a high antiviral activity with IC 50 of 2.92 μM. Besides, honokiol significantly decreased the viral titre and suppressed apoptosis caused by MSRV. Mechanistically, honokiol primarily inhibited the initial replication of MSRV and discharge of progeny virus to exert anti-MSRV activity. More importantly, in vivo experiments suggested that honokiol (40 mg/kg) expressed a fine antiviral activity against MSRV when administrated with intraperitoneal injection, which led to a notable 40% improvement in the survival rate among infected largemouth bass. In addition, it also resulted in significant reduction in the viral nucleic acid expression within liver, spleen and kidney at 2, 4 and 6 days following infection. What is more, 100 mg/kg honokiol with oral administration also showed certain antiviral efficacy in MSRV-infected largemouth bass via improving the survival rate by 10.0%, and decreasing significantly the viral nucleic acid expression in liver, spleen and kidney of largemouth bass on day 2. In summary, natural product honokiol is a good candidate to resist MSRV infection and has promising application prospects in aquaculture.
研究领域:
水产养殖学
·
病毒学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
VIRUS RESEARCH
·
2020
·
IF 2.934
Yu-Feng Shen,Yi-Hang Liu,Bo-Yang Li,Tian-Qiang Liu,Gao-Xue Wang
Rhabdoviruses cause devastating diseases in aquaculture, resulting in enormous economic losses. Our previous studies indicated that imidazole arctigenin derivatives possessed antiviral activities against aquatic rhabdoviruses. Based on the data of structure-activity relationship, a new imidazole arctigenin derivative, 4-(8-(2-bromoimidazole)octyloxy)-arctigenin (BOA), was designed and synthesized. And its antiviral activities against aquatic rhabdoviruses (SVCV, IHNV and MSRV) were evaluated in vitro . By comparing inhibitory concentration at half-maximal activity (IC 50 ), we found that BOA (IC 50 = 1.11 μM) possessed a higher anti-IHNV activity than the antiviral imidazole arctigenin derivatives which were found in our previous study. Besides, BOA could cause profound inhibition of SVCV and MSRV replication. By the reduction assays on cytopathic effect, BOA exhibited a protective effect on two host cell lines. As a typical rhabdovirus, SVCV was chosen as a model to illuminate the anti-rhabdovirus mechanism of BOA. BOA was discovered to not impact directly on viral particles or interfere with SVCV adsorption. And it worked within the 2−6 h of the early phase of virus replication. In addition, after repression of cell cycle S phase and recovery of caspase-3/8/9 activities activated by SVCV, BOA inhibited SVCV-induced apoptosis and then reduced the release of viral particles at the late stage of virus replication. Altogether, BOA was expected to be a highly efficient antiviral agent against multiple rhabdoviruses in the field of aquaculture.
研究领域:
水产养殖
·
病毒学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）