Bis-Benzylisoquinoline Alkaloids Inhibit Porcine Epidemic Diarrhea Virus In Vitro and In Vivo
Shijuan Dong,
Ruisong Yu,
Xiaoting Wang,
Bingqing Chen,
Fusheng Si,
Jiaming Zhou,
Chunfang Xie,
Zhen Li,
Daojing Zhang
Affiliations
Shijuan Dong
Institute of Animal Husbandry and Veterinary Science, Shanghai Key Laboratory of Agricultural Genetics and Breeding, Shanghai Engineering Research Center of Breeding Pig, Shanghai Academy of Agricultural Sciences (SAAS), Shanghai 201106, China
Ruisong Yu
Institute of Animal Husbandry and Veterinary Science, Shanghai Key Laboratory of Agricultural Genetics and Breeding, Shanghai Engineering Research Center of Breeding Pig, Shanghai Academy of Agricultural Sciences (SAAS), Shanghai 201106, China
Xiaoting Wang
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology (ECUST), Shanghai 200237, China
Bingqing Chen
Institute of Animal Husbandry and Veterinary Science, Shanghai Key Laboratory of Agricultural Genetics and Breeding, Shanghai Engineering Research Center of Breeding Pig, Shanghai Academy of Agricultural Sciences (SAAS), Shanghai 201106, China
Fusheng Si
Institute of Animal Husbandry and Veterinary Science, Shanghai Key Laboratory of Agricultural Genetics and Breeding, Shanghai Engineering Research Center of Breeding Pig, Shanghai Academy of Agricultural Sciences (SAAS), Shanghai 201106, China
Jiaming Zhou
Shanghai Jinshan District Animal Center of Disease Control, Shanghai 201540, China
Chunfang Xie
Institute of Animal Husbandry and Veterinary Science, Shanghai Key Laboratory of Agricultural Genetics and Breeding, Shanghai Engineering Research Center of Breeding Pig, Shanghai Academy of Agricultural Sciences (SAAS), Shanghai 201106, China
Zhen Li
Institute of Animal Husbandry and Veterinary Science, Shanghai Key Laboratory of Agricultural Genetics and Breeding, Shanghai Engineering Research Center of Breeding Pig, Shanghai Academy of Agricultural Sciences (SAAS), Shanghai 201106, China
Daojing Zhang
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology (ECUST), Shanghai 200237, China
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 μM, 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.
