药物抗牛病毒性腹泻病毒的研究进展
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摘要
目前,牛病毒性腹泻病毒(BVDV)感染尚无特异性的预防疫苗、治疗方法和抗病毒药物,开发针对牛病毒性腹泻的新型有效药物势在必行。然而,药物抗BVDV的作用机制及靶点不够明确,应用于治疗动物疾病是否有效没有针对性研究,一直以来是制约开发更多的抗BVDV药物的瓶颈问题。文章总结了BVDV侵染细胞机制、药物抗BVDV作用途径,对药物抗BVDV作用进行阐述,以期为药物抗BVDV作用机制研究提供参考,为开发更多有效、低毒、无耐药性的药物提供思路与借鉴。
At present, there is no specific vaccine, treatment, and antiviral drug for bovine viral diarrhea virus(BVDV) infection.It is necessary to develop a new effective drug for treating bovine viral diarrhea-mucosal disease. However, the mechanism and target of drug resistance to BVDV are not clear enough. There is no targeted study on the effectiveness of a drug against animal diseases, and it has always been a bottleneck problem that restricts the development of more anti-BVDV drugs.This paper summarizes the mechanism of BVDV infection cells and the action path of drug resistance to BVDV, and expounds the effect of drug resistance to BVDV, in order to provide reference for mechanism study of anti-BVDV drugs. It will provide ideas and references for developing more effective, low-toxicity and drug-resistant pharmaceutical preparations.
At present, there is no specific vaccine, treatment, and antiviral drug for bovine viral diarrhea virus(BVDV) infection.It is necessary to develop a new effective drug for treating bovine viral diarrhea-mucosal disease. However, the mechanism and target of drug resistance to BVDV are not clear enough. There is no targeted study on the effectiveness of a drug against animal diseases, and it has always been a bottleneck problem that restricts the development of more anti-BVDV drugs.This paper summarizes the mechanism of BVDV infection cells and the action path of drug resistance to BVDV, and expounds the effect of drug resistance to BVDV, in order to provide reference for mechanism study of anti-BVDV drugs. It will provide ideas and references for developing more effective, low-toxicity and drug-resistant pharmaceutical preparations.
引文
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[3] BHUYAN A A,MEMON A M,BHUIYAN A A,et al.The construction of recombinant Lactobacillus casei,expressing BVDV E2 protein and its immune response in mice[J].J Biotechnol,2018,270(1):217.
[4] EVANS C A,LANYON S R,SIMSS K,et al.Reproductive performance in experimentally BVDV infected ewes and seroconversion rates in sheep co-mingled with BVDV PI calves[J].Small Ruminant Res,2015,123(2/3):314-319.
[5] WEI N,QIAO J,MA Q,et al.Development of sheep kidney cells with increased resistance to different subgenotypes of BVDV-1 by RNA interference[J].J Virol Methods,2015,218:66.
[6] LM E A,THOMAS C,LUKE J,et al.Enhanced neutralising antibody response to bovine viral diarrhoea virus (BVDV) induced by DNA vaccination in calves[J].Vaccine,2015,33(32):4004.
[7] 宫晓炜,郑福英,蔺国珍,等.牛病毒性腹泻病毒侵染细胞机制的研究进展[J].畜牧兽医学报,2012,43(4):503-508.
[8] ZHANG Y Q,LIU H S,XIAO-DONG W U,et al.A novel real-time RT-PCR with TaqMan-MGB probes and its application in detecting BVDV infections in dairy farms[J].J Integr Agric,2015,14(8):1637-1643.
[9] VILLALBA M,FREDERICKSEN F,OTTH C,et al.Transcriptomic analysis of responses to cytopathic bovine viral diarrhea virus-1 (BVDV-1) infection in MDBK cells[J].Mol Immunol,2016,71:192.
[10] NEILL J D,RIDPATH J F.Gene expression changes in BVDV2-infected MDBK cells[J].Biologicals,2003,31(2):97-102.
[11] ALKHERAIF A A,TOPLIFF C L,REDDY J,et al.Type 2 BVDV N(pro) suppresses IFN-1 pathway signaling in bovine cells and augments BRSV replication[J].Virology,2017,507:123.
[12] MKS R,ABDELSALAM K,DARWEESH M F,et al.Both cytopathic and non-cytopathic bovine viral diarrhea virus (BVDV) induced autophagy at a similar rate[J].Vet Immunol Immunopathol,2017,193/194:1-9.
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[15] 韩猛立,黄新,宋天增,等.牛病毒性腹泻病毒与宿主细胞的相互作用研究[J].湖北农业科学,2012,51(8):1519-1523.
[16] TONELLI M,VAZZANA I,TASSO B,et al.Antiviral and cytotoxic activities of aminoarylazo compounds and aryltriazene derivatives[J].Bioorg Med Chem,2009,17(13):4425.
[17] TONELLI M,SIMONE M B,NOVELLI F,et al.Antiviral activity of benzimidazole derivatives Ⅱ antiviral activity of 2-phenylbenzimidazole derivatives[J].Bioorg Med Chem,2010,18(8):2937-2953.
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[19] ENGUEHARD-GUEIFFIER C,MUSIU S,HENRY N,et al.3-Biphenylimidazo[1,2- a ]pyridines or [1,2- b]pyridazines and analogues,novel Flaviviridae,inhibitors[J].Eur J Med Chem,2013,64(6):448-463.
[20] LODDO R,BRIGUGLIO I,CORONA P,et al.Synthesis and antiviral activity of new phenylimidazopyridines and N-benzylidenequinolinamines derived by molecular simplification of phenylimidazo[4,5- g ]quinolines[J].Eur J Med Chem,2014,84(18):8-16.
[21] MUSIU S,LEYSSEN P,FROEYEN M,et al.3-(imidazo[1,2-a:5,4-b′]dipyridin-2-yl)aniline inhibits pestivirus replication by targeting a hot spot drug binding pocket in the RNA-dependent RNA polymerase[J].Antiviral Res,2016,129:99-103.
[22] LODDO R,FRANCESCONI V,LAURINI E,et al.9-Aminoacridine-based agents impair the bovine viral diarrhea virus (BVDV) replication targeting the RNA-dependent RNA polymerase (RdRp)[J].Bioorg Med Chem,2018,26(4):855-868.
[23] TONELLI M,VETTORETTI G,TASSO B,et al.Acridine derivatives as anti-BVDV agents[J].Antiviral Res,2011,91(2):133-141.
[24] PUERSTINGER G,PAESHUYSE J,HERDEWIJN P,et al.Substituted5-benzyl-2-phenyl-5H-imidazo[4,5-c]pyridines:a new class of pestivirus inhibitors[J].Bioorg Med Chem,2006,16(20):5345-5349.
[25] YANAGIDA K,BABA C,BABA M.Inhibition of bovine viral diarrhea virus (BVDV) by mizoribine:synergistic effect of combination with interferon-alpha[J].Antiviral Res,2004,64(3):195-201.
[26] 郝宝成,武凡琳,邢小勇,等.苦马豆素抗牛病毒性腹泻病毒的研究[J].中国农业科学,2014,47(1):170-181.
[27] 郝宝成.家畜疯草中毒解毒药物的研制及疯草中活性成分苦马豆素的抗病毒作用机制研究[D].兰州:甘肃农业大学,2017.
[28] 陈慧.沙冬青种子总黄酮的提取工艺及其生物活性研究[D].兰州:甘肃农业大学,2013.
[29] 邱翔宇,相猛,方梅,等.沙冬青总生物碱体外抗牛病毒性腹泻病毒[J].中国兽医学报,2013,33(12):1855-1859.
[30] 宋泉江.连翘酯苷A对BVDV复制影响及BVDV DNA疫苗初步制备和小鼠免疫效果评价[D].北京:中国农业大学,2017.
[31] 郜玉钢,李学,王士杰,等.鹿源牛病毒性腹泻病毒敏感中药筛选的研究[J].黑龙江畜牧兽医,2011(07上):134-135.
[32] WANG J Y,ZHAO Y L,QIN J H.Research on the efficacy of Chinese herbal compound for bovine viral diarrhea[J].Prog Vet Med,2010,31(11):117-119.
[33] 马跃民.牛病毒性腹泻的中药复方治疗效果研究[J].农业开发与装备,2016(2):153.
[34] CIBULSKI S,RIVERAPATRON M,SUáREZ N,et al.Leaf saponins of Quillaja brasiliensis enhance long-term specific immune responses and promote dose-sparing effect in BVDV experimental vaccines[J].Vaccine,2018,36(1):55-65.
[2] LAUREYNS J.What are the monetary losses by BVDV infection and is control cost-effective?[J].Vet J,2017,223:32-33.
[3] BHUYAN A A,MEMON A M,BHUIYAN A A,et al.The construction of recombinant Lactobacillus casei,expressing BVDV E2 protein and its immune response in mice[J].J Biotechnol,2018,270(1):217.
[4] EVANS C A,LANYON S R,SIMSS K,et al.Reproductive performance in experimentally BVDV infected ewes and seroconversion rates in sheep co-mingled with BVDV PI calves[J].Small Ruminant Res,2015,123(2/3):314-319.
[5] WEI N,QIAO J,MA Q,et al.Development of sheep kidney cells with increased resistance to different subgenotypes of BVDV-1 by RNA interference[J].J Virol Methods,2015,218:66.
[6] LM E A,THOMAS C,LUKE J,et al.Enhanced neutralising antibody response to bovine viral diarrhoea virus (BVDV) induced by DNA vaccination in calves[J].Vaccine,2015,33(32):4004.
[7] 宫晓炜,郑福英,蔺国珍,等.牛病毒性腹泻病毒侵染细胞机制的研究进展[J].畜牧兽医学报,2012,43(4):503-508.
[8] ZHANG Y Q,LIU H S,XIAO-DONG W U,et al.A novel real-time RT-PCR with TaqMan-MGB probes and its application in detecting BVDV infections in dairy farms[J].J Integr Agric,2015,14(8):1637-1643.
[9] VILLALBA M,FREDERICKSEN F,OTTH C,et al.Transcriptomic analysis of responses to cytopathic bovine viral diarrhea virus-1 (BVDV-1) infection in MDBK cells[J].Mol Immunol,2016,71:192.
[10] NEILL J D,RIDPATH J F.Gene expression changes in BVDV2-infected MDBK cells[J].Biologicals,2003,31(2):97-102.
[11] ALKHERAIF A A,TOPLIFF C L,REDDY J,et al.Type 2 BVDV N(pro) suppresses IFN-1 pathway signaling in bovine cells and augments BRSV replication[J].Virology,2017,507:123.
[12] MKS R,ABDELSALAM K,DARWEESH M F,et al.Both cytopathic and non-cytopathic bovine viral diarrhea virus (BVDV) induced autophagy at a similar rate[J].Vet Immunol Immunopathol,2017,193/194:1-9.
[13] 李家伟.自噬对不同生物型牛病毒性腹泻病毒感染宿主细胞的作用研究[D].长春:吉林农业大学,2017.
[14] FREDERICKSEN F,CARRASCO G,VILLABA M,et al.Cytopathic BVDV-1 strain induces immune marker production in bovine cells through the NF-κB signaling pathway[J].Mol Immunol,2015,68(2 PtA):213.
[15] 韩猛立,黄新,宋天增,等.牛病毒性腹泻病毒与宿主细胞的相互作用研究[J].湖北农业科学,2012,51(8):1519-1523.
[16] TONELLI M,VAZZANA I,TASSO B,et al.Antiviral and cytotoxic activities of aminoarylazo compounds and aryltriazene derivatives[J].Bioorg Med Chem,2009,17(13):4425.
[17] TONELLI M,SIMONE M B,NOVELLI F,et al.Antiviral activity of benzimidazole derivatives Ⅱ antiviral activity of 2-phenylbenzimidazole derivatives[J].Bioorg Med Chem,2010,18(8):2937-2953.
[18] CHEZAL J M,PAESHUYSE J,GAUMET V,et al.Synthesis and antiviral activity of an imidazo[1,2-a]pyrrolo[2,3-c]pyridine series against the bovine viral diarrhea virus[J].Eur J Med Chem,2010,41(32):2044-2047.
[19] ENGUEHARD-GUEIFFIER C,MUSIU S,HENRY N,et al.3-Biphenylimidazo[1,2- a ]pyridines or [1,2- b]pyridazines and analogues,novel Flaviviridae,inhibitors[J].Eur J Med Chem,2013,64(6):448-463.
[20] LODDO R,BRIGUGLIO I,CORONA P,et al.Synthesis and antiviral activity of new phenylimidazopyridines and N-benzylidenequinolinamines derived by molecular simplification of phenylimidazo[4,5- g ]quinolines[J].Eur J Med Chem,2014,84(18):8-16.
[21] MUSIU S,LEYSSEN P,FROEYEN M,et al.3-(imidazo[1,2-a:5,4-b′]dipyridin-2-yl)aniline inhibits pestivirus replication by targeting a hot spot drug binding pocket in the RNA-dependent RNA polymerase[J].Antiviral Res,2016,129:99-103.
[22] LODDO R,FRANCESCONI V,LAURINI E,et al.9-Aminoacridine-based agents impair the bovine viral diarrhea virus (BVDV) replication targeting the RNA-dependent RNA polymerase (RdRp)[J].Bioorg Med Chem,2018,26(4):855-868.
[23] TONELLI M,VETTORETTI G,TASSO B,et al.Acridine derivatives as anti-BVDV agents[J].Antiviral Res,2011,91(2):133-141.
[24] PUERSTINGER G,PAESHUYSE J,HERDEWIJN P,et al.Substituted5-benzyl-2-phenyl-5H-imidazo[4,5-c]pyridines:a new class of pestivirus inhibitors[J].Bioorg Med Chem,2006,16(20):5345-5349.
[25] YANAGIDA K,BABA C,BABA M.Inhibition of bovine viral diarrhea virus (BVDV) by mizoribine:synergistic effect of combination with interferon-alpha[J].Antiviral Res,2004,64(3):195-201.
[26] 郝宝成,武凡琳,邢小勇,等.苦马豆素抗牛病毒性腹泻病毒的研究[J].中国农业科学,2014,47(1):170-181.
[27] 郝宝成.家畜疯草中毒解毒药物的研制及疯草中活性成分苦马豆素的抗病毒作用机制研究[D].兰州:甘肃农业大学,2017.
[28] 陈慧.沙冬青种子总黄酮的提取工艺及其生物活性研究[D].兰州:甘肃农业大学,2013.
[29] 邱翔宇,相猛,方梅,等.沙冬青总生物碱体外抗牛病毒性腹泻病毒[J].中国兽医学报,2013,33(12):1855-1859.
[30] 宋泉江.连翘酯苷A对BVDV复制影响及BVDV DNA疫苗初步制备和小鼠免疫效果评价[D].北京:中国农业大学,2017.
[31] 郜玉钢,李学,王士杰,等.鹿源牛病毒性腹泻病毒敏感中药筛选的研究[J].黑龙江畜牧兽医,2011(07上):134-135.
[32] WANG J Y,ZHAO Y L,QIN J H.Research on the efficacy of Chinese herbal compound for bovine viral diarrhea[J].Prog Vet Med,2010,31(11):117-119.
[33] 马跃民.牛病毒性腹泻的中药复方治疗效果研究[J].农业开发与装备,2016(2):153.
[34] CIBULSKI S,RIVERAPATRON M,SUáREZ N,et al.Leaf saponins of Quillaja brasiliensis enhance long-term specific immune responses and promote dose-sparing effect in BVDV experimental vaccines[J].Vaccine,2018,36(1):55-65.