Bis-Benzylisoquinoline Alkaloids Inhibit Porcine Epidemic Diarrhea Virus by Disrupting Virus Entry

被引：5

作者：

Zhang, Caisheng ^{[1
,2
]}

Chen, Huan ^{[1
,2
]}

Sun, Liumei ^{[3
]}

Zhao, Pu ^{[1
,2
]}

Qi, Chuanxiang ^{[1
,2
]}

Yang, Ying ^{[1
,2
]}

Si, Anqi ^{[1
,2
]}

Qian, Yingjuan ^{[1
,2
,4
]}

Jung, Yong-Sam ^{[1
,2
]}

机构：

[1] Nanjing Agr Univ, Coll Vet Med, One Hlth Lab, Jiangsu Foreign Expert Workshop, Nanjing 210095, Peoples R China

[2] Nanjing Agr Univ, Coll Vet Med, MOE Joint Int Res Lab Anim Hlth & Food Safety, Nanjing 210095, Peoples R China

[3] Jiangsu Univ Sci & Technol, Sch Biotechnol, Jiangsu Key Lab Sericultural Biol & Biotechnol, Zhenjiang 212100, Peoples R China

[4] Jiangsu Agri Anim Husb Vocat Coll, Jiangsu Key Lab High Tech Res & Dev Vet Biopharmac, Vet Biopharmaceut, Taizhou 225300, Peoples R China

来源：

PATHOGENS | 2023年 / 12卷 / 06期

基金：

中国国家自然科学基金;

关键词：

berbamine; fangchinoline; (+)-fangchinoline; PEDV entry; lysosome acidification; CATHEPSIN-L; CORONAVIRUS; INFECTION; CELLS;

D O I：

10.3390/pathogens12060845

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

The porcine epidemic diarrhea virus (PEDV), belonging to the & alpha;-coronavirus, is the causative agent of porcine epidemic diarrhea (PED). Presently, protection from the existing PEDV vaccine is not effective. Therefore, anti-PEDV compounds should be studied. Berbamine (BBM), Fangchinoline (FAN), and (+)-Fangchinoline (+FAN), are types of bis-benzylisoquinoline alkaloids that are extracted from natural medicinal plants. These bis-benzylisoquinoline alkaloids have various biological activities, including antiviral, anticancer, and anti-inflammatory properties. In this study, we found that BBM, FAN, and +FAN suppressed PEDV activity with a 50% inhibitory concentration of 9.00 & mu;M, 3.54 & mu;M, and 4.68 & mu;M, respectively. Furthermore, these alkaloids can decrease the PEDV-N protein levels and virus titers in vitro. The time-of-addition assay results showed that these alkaloids mainly inhibit PEDV entry. We also found that the inhibitory effects of BBM, FAN, and +FAN on PEDV rely on decreasing the activity of Cathepsin L (CTSL) and Cathepsin B (CTSB) by suppressing lysosome acidification. Taken together, these results indicated that BBM, FAN, and +FAN were effective anti-PEDV natural products that prevented PEDV entry and may be considered novel antiviral drugs.

引用

页数：15

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