青蒿素与牛病毒性腹泻病毒NS5B蛋白的分子对接预测及其抗病毒作用

doi:10.16431/j.cnki.1671-7236.2022.09.032

Abstract

Abstract: 【Objective】 The study was aimed to determine the inhibitory effect of artemisinin on Bovine viral diarrhea virus (BVDV) replication using molecular docking as well as in vitro tests, and provide new ideas for antiviral drug and formulation development.【Method】 BVDV-NS5B protein was used as the target, and the three-dimensional crystal structure of BVDV-NS5B protein was retrieved through the PDB database, and the structure was appropriately modified.The structure of artemisinin from TCMSP database was retrieved, and Autodock software was applied to perform molecular docking and score the binding energy.The maximum safe concentration of artemisinin for MDBK cells was subsequently determined using a CCK-8 kit.The selected concentrations of artemisinin were subjected to gradient dilution, and three different ways of spiking drugs, including adding virus before adding drug, adding drug before adding virus, and the simultaneous action of traditional Chinese medicine and virus, were used for drug antiviral test to determine the optimal drug inhibitory concentration, prophylactic concentration and killing concentration against virus.Real-time quantitative PCR was used to measure the copy number of BVDV under the three modes of drug action to further define the effect of drugs on BVDV replication.【Result】 Molecular docking data indicated that artemisinin interacted with BVDV-NS5B with a binding free energy of -28.6748 kJ/mol.The optimal drug safety concentration of artemisinin on MDBK cells was 100 μmol/L.The three modes of action could effectively affect the replication of BVDV, and artemisinin had the most obvious inhibitory effect on BVDV.【Conclusion】 Artemisinin could interact with the NS5B protein target of BVDV, and could effectively inhibit the replication of BVDV in MDBK cells.This study laid a foundation for the screening of anti BVDV traditional Chinese medicine.

Key words: artemisinin; Bovine viral diarrhea virus (BVDV); antiviral activity; molecular docking; virus replication

CLC Number:

S859.3

SHAO Baihui, JIANG Dongjun, XIE Yimeng, LIU Siyu, SHAO Ziyi, ZHANG Zecai, JI Hong, ZHU Zhanbo. Molecular Docking Prediction of Artemisinin and NS5B Protein of Bovine Viral Diarrhea Virus and Its Antiviral Effect[J]. China Animal Husbandry and Veterinary Medicine, 2022, 49(9): 3581-3588.

References

[1] WERNIKE K, EER M.International proficiency trial for Bovine viral diarrhea virus (BVDV) antibody detection:Limitations of milk serology[J].BMC Veterinary Research, 2022, 18(1):168.
[2] KOETHE S, KÖNIG P, WERNIKE K, et al.A synthetic modified live chimeric marker vaccine against BVDV-1 and BVDV-2[J].Vaccines(Basel), 2020, 8(4):577.
[3] SU A, FU Y, MEENS J, et al.Infection of polarized bovine respiratory epithelial cells by Bovine viral diarrhea virus (BVDV)[J]. Virulence, 2021, 12(1):177-187.
[4] DUAN H, MA Z, XU L, et al.A novel intracellularly expressed NS5B specific nano body suppresses Bovine viral diarrhea virus replication[J]. Veterinary Microbiology, 2020, 240:108449.
[5] BUCKLOWD V E, BEER B E, DONIS R O.Bovine viral diarrhea virus as a surrogate model of Hepatitis C virus for the evaluation of antiviral agents[J].Antiviral Research, 2003, 60(1):1-15.
[6] BELLLIDO D, BAZTARRICAA J, ROCHA L, et al.A novel MHCⅡ targeted BVDV subunit vaccine inducesa neutralizing immunological response in guinea pigs and cattle[J].Transboundary and Emerging Diseases, 2021, 68(6):3474-3481.
[7] 张康, 张凯, 王磊, 等.中药抗牛病毒性腹泻病毒研究进展[J].中兽医药杂志, 2019, 38(6):23-26. ZHANG K, ZHANG K, WANG L, et al.Research progress on antibovine viral diarrhea virus in traditional Chinese medicine[J].Chinese Journal of Veterinary Medicine, 2019, 38(6):23-26.(in Chinese)
[8] ZIERCOK A K, MCZKA W K, GRABARCZVK M, et al.Isoxanthohumol——Biologically active hop flavonoid[J].Fitoterapia, 2015, 103:71-82.
[9] 王旭刚.青蒿素抑制黄病毒复制及其机制研究[D].武汉:华中农业大学, 2020. WANG X G.Artemisinin inhibition of Flavivirus replication and its mechanism[D].Wuhan:Huazhong Agricultural University, 2020.(in Chinese)
[10] MUNYANDUKI H, OMAR R, DOUGLASS N, et al.Removal of Bovine viral diarrhea virus (BVDV) from Lumpy skin disease virus (LSDV) vaccine stocks by passage on chorioallantoic membranes of fertilized hens' eggs[J].Journal of Virological Methods, 2020, 275:113752.
[11] 卞娅, 葛广波, 丁侃.中药多糖抗病毒机制研究进展[J].上海中医药大学学报, 2021, 35(5):89-96. BIAN Y, GE G B, DING K. Research progress on the antiviral mechanism of polysaccharides in traditional Chinese medicine[J]. Journal of Shanghai University of Traditional Chinese Medicine, 2021, 35(5):89-96.(in Chinese)
[12] 栗昀.冰香散及其主要成分1, 8-cineol防治流感实验研究[D].广州:广州中医药大学, 2017. LI Y.Experimental study on influenza prevention and control of 1, 8-cineol and its main component[D].Guangzhou:Guangzhou University of Traditional Chinese Medicine, 2017.(in Chinese)
[13] AlKUBATI A A G, HUSSEN J, KANDEEL M, et al.Recent advances on the Bovine viral diarrhea virus molecular pathogenesis, immune response, and vaccines development[J].Frontiers in Veterinary Science, 2021, 14, 8:665128.
[14] 阎祖炜, 朱欣, 李闻文.MTT法、CPE观察法用于药物细胞毒性实验的比较与分析[J].实用预防医学, 2007, 5:1552. YAN Z W, ZHU X, LI W W.Comparison and analysis of MTT method and CPE observation method for drug cytotoxicity experiments[J]. Practical Preventive Medicine, 2007, 5:1552.(in Chinese)
[15] 蔡文涛.MTT法和CCK-8法检测中药抗病毒活性成分细胞毒性的比较[J].湖北大学学报(自然科学版), 2017, 39(3):305-310. CAI W T.Comparison of cytotoxicity of antiviral active ingredients in traditional Chinese medicines by MTT method and CCK-8 method[J].Journal of Hubei University(Natural Science Edition), 2017, 39(3):305-310.(in Chinese)
[16] 徐培平, 赵昉, 刘妮, 等.中药体外防治甲型H1N1流感病毒实验研究[J].实用预防医学, 2012, 19(8):1121-1124. XU P P, ZHAO F, LIU N, et al.In vitro study on preventive effects of three Chinese medicines against Influenza A (H1N1)[J]. Practical Preventive Medicine, 2012, 19(8):1121-1124.(in Chinese)
[17] 雷湘, 陈科力, 杨占秋, 等.大黄素配伍对柯萨奇病毒B3感染小鼠的病毒抑制作用研究[J].中药药理与临床, 2019, 35(1):121-126. LEI X, CHEN K L, YANG Z Q, et al.Viral inhibition effect of emodin compatibility on Coxsackievirus B3 infected mice[J]. Pharmacology and Clinical Practice of Traditional Chinese Medicines, 2019, 35(1):121-126.(in Chinese)
[18] 张春江, 李薇, 孙振鹏, 等.藏药甘青乌头抗单纯疱疹病毒Ⅱ型体内体外作用研究[J].中国医药学杂志., 2009, 44(1):26-31. ZHANG C J, LI W, SUN Z P, et al.Study on the internal and external functions of Tibetan medicine Ganqing Aconitum anti-herpes simplex virus type Ⅱ[J]. Chinese Pharmaceutical Miscellaneous, 2009, 44(1):26-31.(in Chinese)
[19] 杨丽华.藏药甘青乌头中二萜生物碱的研究[D].广州:广东药科大学, 2016. YANG L H.Study on diterpene alkaloids in Tibetan medicine Ganqing Aconitum[D].Guangzhou:Guangdong Pharmaceutical University, 2016.(in Chinese)
[20] 刘璐, 吴立军, 杨春娟.紫堇属植物中异喹啉类生物碱的化学结构和生物活性的研究进展[J].实用药物与临床, 2016, 19(3):371-380. LIU L, WU L J, YANG C J.Research progress on chemical structure and biological activity of is oquinoline alkaloids in violet[J].Practical Drugs and Clinical Medicines, 2016, 19(3):371-380.(in Chinese)
[21] SILVIA M, ALESSANDRA M, GIUSEPPINA S, et al.Bovine viral diarrhea virus (BVDV):A preliminary study on antiviral properties of some aromatic and medicinal plants[J] .Pathogens, 2021, 10(4):403.
[22] 王慧, 杜锐, 周红潮, 等.中药抗牛病毒性腹泻病毒作用研究现状[J].动物医学进展, 2018, 39(2):123-126. WANG H, DU R, ZHOU H C, et al.Research status of antibovine viral diarrhea virus in traditional Chinese medicine[J].Advancesin Veterinary Medicine, 2018, 39(2):123-126.(in Chinese)
[23] HUANG K, ZHANG P, ZHANG Z H, et al.Traditional Chinese medicine (TCM) in the treatment of viral infections:Efficacies and mechanisms[J].Pharmacology & Therapeutics, 2021, 225:107843.

Molecular Docking Prediction of Artemisinin and NS5B Protein of Bovine Viral Diarrhea Virus and Its Antiviral Effect

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	FAN Yimeng, WEI Yuanyuan, WANG Huiru, GA yu, ZHANG Yannan, ZHAO Qingyu, HAO Zhihui. Potential Mechanisms of Chinese Veterinary Medicine Compound Rukang Granules in the Treatment of Dairy Cow Mastitis Based on Network Pharmacology and Molecular Docking Technology [J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(6): 2507-2517.
[2]	ZHAO Qianhui, LIU Ying, JIAO Yulan, SHI Wanyu, CHEN Fuxing. Exploring of the Mechanism of Cuscuta chinensis Flavonoids in Alleviating Reproductive Damage in Offspring Rats Exposed to Bisphenol A During Pregnancy Based on Network Pharmacology [J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(6): 2550-2561.
[3]	ZHANG Xinyue, SUN Na, SUN Panpan, ZHANG Hua, FAN Kuohai, YIN Wei, SUN Yaogui, LI Hongquan. Mechanism of Scutellarin Against Follicular Atresia Based on Network Pharmacology and Molecular Docking [J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(6): 2585-2593.
[4]	XU Chenghui, ZHANG Xumei, YANG Tong, LI Jiahui, SUN Yawei, SHI Huijun, FU Qiang, YANG Li. Molecular Mechanism of Leonurine in the Treatment of Intestinal Inflammation Based on Network Pharmacology and Molecular Docking [J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(5): 2103-2113.
[5]	LIU Xinyu, CUI Qiang, ZHANG Lanxin, FAN Quanrong, LI Zhengyi, GAO Ruifeng. Study on Mechanism of Chebulagic Acid in Treatment of Cow Endometritis Based on Network Pharmacology and Molecular Docking [J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(4): 1632-1641.
[6]	LIU Kexin, WANG Chao, ZHANG Ao, LIU Jiali, TAN Bin, ZHANG Shuqin. Isolation,Identification and Genome Sequence Analysis of Bovine Viral Diarrhea Virus LN-1 Strain [J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(3): 1150-1159.
[7]	DOU Jiahong, WANG Ziying, YANG Juan, ZHOU Weiwei, ZHANG Tongcun, HE Hongpeng, DAI Xiaofeng, LI Xiumei. Analysis of the Active Ingredients and Mechanism of Radix Paeoniae Rubra Antioxidative Stress Based on Network Pharmacology and Molecular Docking [J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(3): 1229-1240.
[8]	HAN Guorui, XIAO Xiaoyue, ZHANG Yang, LI Yanhua, CHEN Xueying, WANG Xiumin, QIN Junjie, LIU Yanyan. Mechanism of Gui Qi Yimu Oral Liquid in the Treatment of Sus scrofa Qi and Blood Two Deficiency Syndrome Based on Network Pharmacology and Molecular Docking [J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(2): 722-733.
[9]	XIA Jinjin, YU Jie, LI Yana, LIU Jiali, YAN Pupu, CHEN Xiaolan, GUO Liwei. Study on the Mechanism of Mahuang Gancao Decoction in Treating Pulmonary Edema Based on Network Pharmacology [J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(2): 764-778.
[10]	SUN Panpan, HOU Zhen, HAO Zhili, ZHENG Jiangang, SUN Na, FAN Kuohai, YIN Wei, LI Hongquan. Study on Mechanism of Curcumol Against Encephalomyocarditis Virus Based on Network Pharmacology and Molecular Docking [J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(1): 341-348.
[11]	ZHANG Zufeng, ZHANG Yuxin, SUN Yuelong, ZHENG Wei, LI Xiumei. Study on Mechanism of Hawthorn in Regulating Oxidative Stress Based on Network Pharmacology and Molecular Docking [J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(1): 408-420.
[12]	WANG Wei, HAN Huihui, DING Naizheng, HE Chengqiang. Prokaryotic Expression of Bovine Viral Diarrhea Virus E0 Protein and Preparation of Polyclonal Antibody [J]. China Animal Husbandry and Veterinary Medicine, 2022, 49(8): 3131-3139.
[13]	SONG Shiying, GUO Weilu, XIA Xuefeng, ZHANG Xue, BI Zhenwei, ZHANG Xuehan, FAN Baochao, DONG Hailong, LI Bin. Expression and Purification of Porcine IFN-δ5 and Its Effect Analysis Against PEDV Infection [J]. China Animal Husbandry and Veterinary Medicine, 2022, 49(8): 3171-3179.
[14]	SUN Yuelong, ZHANG Mengjie, DOU Jiahong, WANG Xiaoying, DAI Xiaofeng, LI Xiumei. Effects of Astragalus membranaceus (Fisch.) Bunge.on Piglets Flora Imbalance Diarrhea Based on Network Pharmacology and Molecular Docking [J]. China Animal Husbandry and Veterinary Medicine, 2022, 49(8): 3200-3211.
[15]	REN Jie, LIN Ling, TANG Deyuan, ZENG Zhiyong, WANG Bin, YU Guangmei, ZHENG Ruwen, WU Daoyi, HUANG Tao. Construction of Bovine Viral Diarrhea Virus E0-E2 Gene Fusion Adenovirus and Evaluation of Immune Effect in Mice [J]. China Animal Husbandry and Veterinary Medicine, 2022, 49(6): 2056-2063.