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Bis-Benzylisoquinoline Alkaloids Inhibit Porcine Epidemic Diarrhea Virus In Vitro and In Vivo

文献类型： 外文期刊

作者： Dong, Shijuan 1 ; Yu, Ruisong 1 ; Wang, Xiaoting 2 ; Chen, Bingqing 1 ; Si, Fusheng 1 ; Zhou, Jiaming 3 ; Xie, Chunfang 1 ; Li, Zhen 1 ; Zhang, Daojing 2 ;

作者机构： 1.Shanghai Acad Agr Sci SAAS, Shanghai Engn Res Ctr Breeding Pig, Inst Anim Husb & Vet Sci, Shanghai Key Lab Agr Genet & Breeding, Shanghai 201106, Peoples R China

2.East China Univ Sci & Technol ECUST, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

3.Shanghai Jinshan Dist Anim Ctr Dis Control, Shanghai 201540, Peoples R China

关键词： PEDV; bis-benzylisoquinoline alkaloids; cepharanthine; tetrandrine; fangchinoline; antiviral effect; in vitro; in vivo

期刊名称：VIRUSES-BASEL （ 影响因子：5.818； 五年影响因子：5.811 ）

ISSN：

年卷期： 2022 年 14 卷 6 期

页码：

收录情况： SCI

摘要： Porcine epidemic diarrhea virus (PEDV) belongs to the genus Alphacoronavirus of the family Coronaviridae that causes severe diarrhea and high mortality in neonatal suckling piglets. Currently, there is no effective medication against this pathogen. Cepharanthine (CEP), tetrandrine (TET), and fangchinoline (FAN) are natural bis-benzylisoquinoline alkaloids with anti-inflammatory, antitumor, and antiviral properties. Here, we first found that CEP, TET, and FAN had anti-PEDV activity with IC50 values of 2.53, 3.50, and 6.69 mu M, respectively. The compounds could block all the processes of viral cycles, but early application of the compounds before or during virus infection was advantageous over application at a late stage of virus replication. FAN performed inhibitory function more efficiently through interfering with the virus entry and attachment processes or through attenuating the virus directly. CEP had a more notable effect on virus entry. With the highest SI index of 11.8 among the three compounds, CEP was chosen to carry out animal experiments. CEP in a safe dosage of 11.1 mg/kg of body weight could reduce viral load and pathological change of piglet intestinal tracts caused by PEDV field strain challenge, indicating that CEP efficiently inhibited PEDV infection in vivo. All of these results demonstrated that the compounds of bis-benzylisoquinoline alkaloids could inhibit PEDV proliferation efficiently and had the potential of being developed for PED prevention and treatment.

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